**Metals in Medicine: Targets, Diagnostics, and Therapeutics**

**June 28 & 29, 2000**

**Natcher Conference Center**

**National Institutes of Health**

**Bethesda, Maryland, U.S.A.**

**Contents:**

Introduction\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\.....3

Final
Agenda\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...5

List of
Speakers\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\.....9

List of
Posters\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\.....11

Speaker
Abstracts\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\.....17

Speaker
Biosketches\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\....45

Poster
Abstracts\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\.....69

Additional
Biosketches\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\....103

List of
Registrants\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...151

**Sponsors:**

National Institute of General Medical Sciences

Center for Scientific Review, NIH

National Cancer Institute

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Allergy and Infections Diseases

National Institute of Environmental Health Sciences

Office of Dietary Supplements, Office of the Director, NIH

**Meeting Website:**
<http://www.nigms.nih.gov/news/meetings/metals.html>

**Meeting Contact:** Dr. Peter C. Preusch, NIGMS. E-mail:
<preuschp@nigms.nih.gov>

**Cover Art:** Paul Ehrlich (1854-1915), a founding figure in medicinal
chemistry and developer of Salvarsan (arsphenamine), one of the first
effective chemotherapeutics \-- an inorganic agent used in the treatment
of syphilis. Structure of HMG1 domain A bound to cisplatin modified DNA,
solved in the laboratory of Stephen J. Lippard.

**Metals in Medicine: Targets, Diagnostics, and Therapeutics**

**INTRODUCTION: Why Metals, Why Here, Why Now?**

The National Institute of General Medical Sciences and other components
of the National Institutes of Health have provided significant support
for research in the areas of bioinorganic chemistry and
metallobiochemistry. Much of the proposed research in this area has been
reviewed by the Metallobiochemistry study section of the Center for
Scientific Review. It is important to insure that this basic research
investment is translated into health benefits. A focused meeting on the
NIH campus was conceived as a way to emphasize NIH interest in the area.
Discussions with leaders in the field suggested that opportunities exist
to increase the impact of the NIH investment in this area through
additional research and enhanced participation of bioinorganic chemists
in the pharmaceutical development process.

Recent advances have occurred in understanding the roles of metals in
cell regulation, the complexities of metal metabolism, and the
mechanisms of metalloenzymes. Metalloenzymes are well recognized as
targets for conventional drug development. Advances have occurred in the
ability to characterize these proteins and to model metal/ligand
interactions in drug design. Advances in understanding metal trafficking
and the roles of metals in disease have suggested targeting metals,
themselves, as a useful therapeutic strategy. The success of cisplatin
and its congeners suggests that metals can also be developed as
therapeutic agents. The ability to synthesize sophisticated metal
complexes has become well established. Advances have occurred in
understanding and controlling the reactivity of metals *in vitro* and
*in vivo*. Experience in the development of imaging and radiation
therapy agents demonstrates that metal complexes can be tailored to
provide clinically useful pharmacokinetic properties. Methods have been
developed that allow metal complexes to target selected cellular and
molecular processes.

The objectives of the meeting are to:

-   Present state-of-the-art research on metal-containing systems of
    medical importance;

-   Identify emerging areas of research opportunity;

-   Increase communication between scientists in academia, government,
    and industry;

-   Foster the formation of new collaborative research efforts in the
    field.

The scientific program is intended to examine the current role of
bioinorganic chemistry in the pharmaceutical industry; examine
opportunities for the development of inorganic complexes as therapeutic
agents and diagnostics; and examine opportunities for the development of
drugs that manipulate endogenous metal metabolism or otherwise exploit
metal-containing targets. Issues in drug development, such as
specificity, stability, and toxicity will be explored. The principles of
medicinal chemistry applicable to the development and regulation of
organic agents have been well developed. It is hoped that a statement of
the principles of medicinal chemistry relevant to metals will emerge
from this meeting, or at least, a statement of the research needed to
elucidate those principles.

The meeting program is currently available interactively through the
Metals in Medicine meeting Web site: <http://pub.nigms.nih.gov/MIM/>.
This site will be maintained for at least several weeks after the
meeting. A printable archive version of this meeting booklet in both
Word and Adobe Acrobat formats will be available through the NIGMS Web
site for the indefinite future. See:
<http://www.nigms.nih.gov/news/meetings/metals.html>. A report of this
meeting will become available on the NIGMS site shortly after the
meeting. Visit the NIGMS site for postings of additional information of
interest as the year progresses. The meeting is being videocast live to
the internet and the NIH local area network (MBONE) via:
[http://videocast.nih.gov](http://videocast.nih.gov/). The videocast
will be available as an archive rebroadcast within a few weeks of the
meeting.

Meeting organized by NIGMS staff. Contact: Peter C. Preusch, Ph.D.,
Pharmacology, Physiology, and Biological Chemistry Division, National
Institute of General Medical Sciences, NIH, 45 Center Drive, MSC 6200,
Bethesda, Maryland, USA, 20892-6200. Phone: 301-594-5938. Fax:
301-480-2802. Email: preuschp@nigms.nih.gov.

Input from other sponsoring NIH components, and suggestions from a
substantial number of the meeting participants and other active
researchers in the field, are gratefully acknowledged. The contributions
of the discussion chairpersons, Stephen J. Lippard, John Kozarich,
Thomas Meade, Thomas V. O\'Halloran, and Nicholas P. Farrell, are
particularly acknowledged.

**FINAL AGENDA**

**METALS IN MEDICINE:**

**Targets, Diagnostics, and Therapeutics**

**DAY 1 - June 28, 2000**

7:30 **Registration**

8:00 **Introduction**: Peter Preusch, Marvin Cassman

(National Institute of General Medical Sciences, NIH)

8:15 **Keynote** **Address**: Case History and Recent Advances in
Understanding Cisplatin

Stephen Lippard (Massachusetts Institute of Technology)

**Session 1: Molecular and Cellular Targets of Metal Action**

9:00 Metal-Catalyzed Cleavage of Nucleic Acids

Cynthia Burrows (University of Utah)

9:30 Selective Inhibition of Human α-Thrombin by Co(III) Schiff Base
Complexes

Thomas Meade (California Institute of Technology)

10:00 Coffee Break

10:30 Metal Complexes and Drug Transport

David Piwnica-Worms (Washington University)

11:00 Metal Complexes as Receptor Ligands

Shubh Sharma (Palatin Technologies, Inc.)

11:30 Session Discussion - Stephen Lippard (Discussion Leader)

12:00 Lunch Break

**Session 2: Metal-Containing Targets of Drug Action**

1:00 Metalloenzyme Drug Development Targets at Merck

John Kozarich (Merck & Company)

1:30 Nitric Oxide Synthase

Thomas Poulos (University of California-Irvine)

2:00 Molecular Modeling Of Metalloenzymes: Current Status And Future
Prospects

Kenneth Merz (Pennsylvania State University)

2:30 Modeling Matrix Metalloproteases: A Case Study

Benjamin Burke (Agouron Pharmaceuticals, Inc.)

3:00 Coffee Break

**Session 3: Radiology, Imaging, and Photodynamic Therapy**

3:30 Fundamentals of Receptor-Based Metalloradiopharmaceuticals

Shuang Liu (DuPont Pharmaceuticals Co.)

4:00 Radiolabeled Somatostatin Analogs for Targeted Radiotherapy of
Cancer

Carolyn Anderson (Washington University)

4:30 Biophysical Tuning and Targeting of Gadolinium(III) Chelates for
MRI

Randall Lauffer (EPIX Medical, Inc.)

5:00 Metallotexaphyrins: New Drugs with Diverse Applications in Cancer
Treatment

Richard Miller (Pharmacyclics, Inc.)

5:30 Discussion Session - John Kozarich, Thomas Meade (Discussion
Leaders)

6:00 Poster Session and Evening Reception

7:30 Meeting Adjourned for the Day

**DAY 2 - June 29, 2000**

**Session 4: Metal Metabolism**

8:30 Intracellular Trafficking Pathways: Inorganic Cell Biology of
Copper and Zinc

Thomas O\'Halloran (Northwestern University)

9:00 Combinatorial RNA Regulation Of Bio-Iron And New Drug Targets

Elizabeth Theil (Children\'s Hospital of Oakland Research Institute)

9:30 Metal Chelation Therapy

Ken Raymond (University of California-Berkeley)

10:00 Coffee Break

10:30 Chromium as a Dietary Supplement

Richard Anderson (U.S. Department of Agriculture)

11:00 Mechanisms of Metal Toxicity

Max Costa (New York University)

11:30 Session Discussion - Thomas O\'Halloran (Discussion Leader)

12:00 Lunch Break

**Session 5: Metallotherapeutics and Disease**

1:00 Vanadium and Diabetes

Christopher Orvig (University of British Columbia)

1:30 Computer-Aided Design Of Selective Synthetic Superoxide Dismutase

Enzyme Mimetics

Dennis Riley (Metaphore Pharmaceuticals, Inc.)

2:00 Polyoxometalate Nanocluster HIV-1 Protease Inhibitors: A New Mode
of

Protease Inhibition

Craig Hill (Emory University)

2:30 NCI Developmental Therapeutics Program Experiences

Jill Johnson (National Cancer Institute, NIH)

3:00 Coffee Break

**Session 6: Medicinal Chemistry of Metallopharmaceuticals**

3:30 Principles of Medicinal Chemistry for Inorganics

Nicholas Farrell (Virginia Commonwealth University)

4:00 The US Drug Approval Process - Challenges for
Metallopharmaceuticals

David Place (Food and Drug Administration)

4:30 The Bicyclam Story: From Metal Complexes to Ligands and Back to
Metal

Complexes

Michael Abrams (AnorMED, Inc.)

5:00 Discussion Session & Closing Comments - Nicholas Farrel (Discussion
Leader)

Peter Preusch & Michael Rogers (National Institute of General Medical
Sciences)

5:30 Meeting Adjourned

**Metals in Medicine: Targets, Diagnostics, and Therapeutics**

**LIST of SPEAKERS (Alphabetically)**

Michael Abrams (AnorMED, Inc.)

Carolyn Anderson (Washington University)

Richard Anderson (United States Department of Agriculture)

Benjamin Burke (Agouron Pharmaceuticals, Inc.)

Cynthia Burrows (University of Utah)

Max Costa (New York University)

Nicholas Farrell (Virgina Commonwealth University)

Craig Hill (Emory University)

Jill Johnson (National Cancer Institute)

John Kozarich (Merck Research Labs)

Randall Lauffer (EPIX Medical, Inc.)

Stephen Lippard (Massachusetts Institute of Technology)

Shuang Liu (DuPont Pharmaceuticals Company)

Thomas Meade (California Institute of Technology)

Kenneth Merz (Pennsylvania State University)

Richard Miller (Pharmacyclics, Inc.)

Thomas O\'Halloran (Northwestern University)

Chrisopher Orvig (University of British Columbia)

David Piwnica-Worms (Washington University)

David Place (Food and Drug Administration)

Thomas Poulos (University of California-Irvine)

Kenneth Raymond (University of California-Berkeley)

Dennis Riley (Metaphore Pharmaceuticals, Inc.)

Shubh Sharma (Palatin Technologies, Inc.)

Elizabeth Theil (Children\'s Hospital of Oakland Research Institute)

Additional Speakers Participating in the Discussion Sessions:

Bruce Averill (University of Amsterdam)

Christopher Frederickson (University of Texas Medical Branch-Galveston)

Jie Liu (National Institute of Environmental Health Sciences)

Susan Doctrow (Eukarion, Inc.)

Janet Morrow (State University of New York at Buffalo)

David Petering (University of Wisconsin-Milwaukee)

**LIST OF POSTERS**

**Submitting Author and Affiliation**

\* Indicates Authors Sharing a Posterboard.

^†^ Indicates Poster and Short Presentation

**By Related Meeting Session:**

**Session 1. Molecular and Cellular Targets of Metal Action**

1.  Binding of HMG-domain Proteins in Purine-Rich Platinated DNA

Seth M. Cohen, Massachusetts Institute of Technology\*

2.  Laser-Induced Photocross-linking of Cisplatin-Modified DNA to Damage
    Recognition Proteins

Yuji Mikata, Massachusetts Institute of Technology\*

3.  Computational Analysis of All the Possible Configurational/Binding
    Geometries of Co(III) Bleomycins

Marc Zimmer, Connecticut College

4.  The Bioinorganic-Biomedical Interface of the Redox Active Antitumor
    Agent Iron Bleomycin

David H. Petering, University of Wisconsin-Milwaukee^†^

5.  \'Fe^2+^ + O~2~\' is More Important than the Fenton Reaction in
    Initiating Biological Radical Oxidation

Steven Y. Qian, National Institutes of Health

6.  Oxidative Cleavage Of DNA Substrates Mediated By Copper Complexes
    With Pyridyl(Alkyl)Amine Ligands

Kristi J. Humphreys, Johns Hopkins University

7.  A Combinatorial Approach to the Discovery of New Metal Complexes for
    Peptide Cleavage

Kathryn B. Grant, Georgia State University

8.  Design Of A Squence-Specific Photonuclease From A Synthetic bZIP
    Metalloprotein.

Robin C. Lasey, Bowling Green State University

9.  Inactivation of mRNA through Cleavage of the 5\'-Cap Structure by
    Metal Ion Complexes and Oligonucleotide Conjugates

Janet R. Morrow, State University of New York at Buffalo^†^

**Session 2. Metal Containing-Targets of Drug Action**

10. Divalent Metal Binding and Mechanism of Action of the Methionine
    Aminopeptidases from *Escherichia Coli* and *Pyrococcus furiosus*

Richard C. Holz, Utah State University\*

11. Redox Regulation of Signal Transduction via Calcineurin

Frank Rusnak, Mayo Clinic & Foundation\*

12. Mycobacterium tuberculosis Catalase/Peroxidase KatG in Isoniazid
    Activation and Resistance

Nancy L. Wengenack, Mayo Clinic & Foundation\*

13. Towards Understanding the Heme Environment Required for Activation
    of Isoniazid by M. Tuberculosis KatG

Kenton R. Rogers, North Dakota State University\*

14. Proteolytic Activation of the Catalytic Activity of Purple Acid
    Phosphatases: A Possible Regulatory Mechanism and Potential
    Therapeutic Target for Treatment of Osteoporosis and Other Disorders

Bruce Averill, E.C. Slater Institute, University of Amsterdam^†^

15. Nature\'s Way to Make Methane

Stephen W. Ragsdale, University of Nebraska

16. The Evolving Mechanism of Metallo-beta-lactamase

Walter Fast, Pennsylvania State University

17. Structure and Chemistry of the Enzyme Active Site of Glyoxalase I

Uwe Richter, National Institute of Standards and Technology

18. Engineering Type-1 Copper Centres In Redox Enzymes For Hot Wiring

Martin Ph. Verbeet, Leiden Institute of Chemistry

19. Identifying And Designing Of Calcium-Binding Proteins

Jenny J. Yang, Georgia State University

20. The Guanidine Moiety as a Ligand for Hemin

Dabney W. Dixon, Georgia State University\*

21. Nitric Oxide Dioxygenases: Efficient Catalysts for Nitric Oxide
    Metabolism in Microbes and Mammals

Paul R. Gardner, Children\'s Hospital Medical Center of Cincinnati\*

**Session 3. Imaging, Radiology, and Photodynamic Therapy**

22. Receptor Based Biosensor for Gallium Using Novel Therapeutic
    Immunoconjugate

Omowunmi A. Sadik, SUNY Binghamton

23. Synthesis and Relaxometric Investigations of Starburst
    Dendrimer-DOTA-M (M=Gd(III), Mn(II), Fe(III))

L. Henry Bryant, Jr., National Institutes of Health

24. Lung Cancer - From Radiodiagnosis to Radiotherapy with Novel
    Somatostatin Receptor-Binding Peptides

Rajeesh Manchanda, Diatide, Inc.

25. MR Tracking of Cell Migration and Myelination Following
    Transplantation of Magtagged Glial Cells

Jeff W.M. Bulte, National Institutes of Health

26. Seeing is Believing: Visualizing In Vivo Gene Expression and
    Secondary Messengers by Magnetic Resonance Imaging

Thomas J. Meade, California Institute of Technology^†^

27. The First Three-Dimensional Perfluorinated Phthalocyanine:
    Synthesis, Structure and Photodynamic Activity

Barbara A. Bench, Brown University

28. Metalloenediynes for Thermal and Photochemical Control of Bergman
    Cyclization

Jeffrey M. Zaleski, Indiana University

**Session 4. Metal Metabolism as a Therapeutic Target**

29. Synaptic Release of Free Zinc Ions in the Brain: Roles in Brain
    Function, Disease, and Injury

Christopher J. Frederickson, University of Texas Medical
Branch-Galveston^†^

30. Fluorescent Peptidyl Platforms for Metal Ion Sensing in Aqueous
    Solution

Dierdre A. Pearce, Massachusetts Institute of Technology\*

31. The Shu S protein of *Shigella dysenteriae* is a Heme-Sequestering
    Protein that Binds and Protects DNA.

Angela Wilks, University of Maryland\*

32. Accelerating Iron Release from Transferrin

Wesley R. Harris, University of Missouri-St. Louis

33. Fe(III) Coordination and Redox Properties of a Bacterial Transferrin

Alvin L. Crumbliss, Duke University

34. Ferritin is a Nuclear Protein that Responds to Cell Stress and
    Protects DNA

Khristy Thompson, Pennsylvania State University at Hershey

35. Investigation of Structure and Metal Binding Properties of
    Transferrins by Electropray Mass Spectrometry

Igor A. Kaltashov, University of Massachusetts

36. Why is lead toxic? Unraveling the Molecular Mechanism(s) of Lead
    Poisoning.

Hilary A. Godwin, Northwestern Univeristy

37. Lead-Filled Tetraplex: Solution and Solid State Studies of
    G-Quartets Bound to Pb^+2^

Jeffery T. Davis, University of Maryland

38. Structural biology of the GMTCXXC consensus sequence in the first
    metal binding domain from the protein involved in Menkes disease,
    MerP, and synthetic peptides.

Tara M. DeSilva, University of Pennsylvania

39. Wilson\'s Disease Protein: Ligand-Binding Properties and
    Copper-Dependent Domain-Domain Interactions

Svetlana Lutsenko, Oregon Health Sciences University

40. Characterization of the Mouse Homologue of a Bacterial Arsenite
    Translocating ATPase

Hiranmoy Bhattacharjee, Wayne State University\*

41. Structure of the ArsA ATPase: the Catalytic Subunit of a Heavy Metal
    Resistance Pump

Tongqing Zhou, Wayne State University\*

42. Application of cDNA Microarray to the Study of Arsenic Toxicology
    and Carcinogenesis

Jie Liu, National Institute of Environmental Health Sciences^†^

**Session 5. Metallotherapeutics and Disease**

43. The Antiviral Activity of Titanyl (TiO^+2^) Sulfate Toward Human
    Cytomegalovirus

Chad W. Schwietert, San Francisco State University

44. Tachpyridine, A Novel Iron Chelator and a Potential Anti-Cancer
    Agent in the Treatment of Tumors with Mutated p53

Suzy V. Torti, Wake Forest University

45. Anti-inflammatory Properties of M40403, a Low Molecular Weight
    Synthetic Superoxide Dismutase Mime

Daniela Salvemini, MetaPhore Pharmaceuticals

46. Salen Mn Complexes, Combined SOD/Catalase Mimics with Broad
    Pharmacological Efficacy, are Protective in Models for
    Neurodegeneration

Susan Doctrow, Eukarion Inc.^†^

47. Peroxynitrite Decomposition Catalyzed by Water-Soluble Iron
    Porphyrins.

Roman Shimanovich, Princeton University

48. Development of Materials for Storage, Release, and Detection of
    Nitric Oxide.

Andrew S. Borovik, University of Kansas

49. Chemistry and Insulin Like Properties of Cobalt
    2,6-pyridinedicarboxylate Complexes

Debbie C. Crans, Colorado State University

50. What Is The Active Vanadium Pool In NIDDM Patients Dosed With
    Vanadyl Sulfate?

Gail Willsky, State University of New York at Buffalo

51. Vanadium and Insulinomimesis: A Possible Role of
    Phosphatidylinositol 3-Kinase

Ashok K. Srivastava, University of Montreal

**Other Topics**

52. NIH Support for Bioinorganic Chemistry

Peter C. Preusch, National Institutes of Health\*

53. In the Beginning... The Evolutionary Origin of Aerobic Metabolism

G. Charles Dismukes, Princeton University\*

SPEAKER ABSTRACTS

(IN ORDER OF PRESENTATION)

**Case History and Recent Advances in Understanding Cisplatin**

Stephen J. Lippard, Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts, USA, 02139.

![](media/image1.wmf){width="3.6944444444444446in"
height="0.8430555555555556in"} *cis*-Diamminedichloroplatinum(II), or
cisplatin, is in widespread use for the treatment of genitourinary, head
and neck, and a variety of other cancers. The discovery of the
anticancer properties of cisplatin arose from a completely serendipitous
finding during experiments designed to probe the effects of electric
fields on cell division. The trans isomer (*trans*-DDP) is inactive.
Following administration by intravenous injection cisplatin is activated
in cells by aquation to form cationic species that bind to DNA. The
major adducts are 1,2-intrastrand cross-links, also formed by
carboplatin, which has fewer dose-limiting side effects. The structural
distortion in DNA that accompanies platination affects replication and
transcription. In particular, the minor groove across from the
cross-link is wide and shallow, creating a hydrophobic notch and surface
that are recognized by various proteins. Included are high-mobility
group (HMG) domain proteins. HMG-domain proteins bind with specificity
to the major cisplatin-DNA adducts, forming a stable
platinum-DNA-protein ternary complex. The X-ray structure of HMG domain
A in HMG1, bound to a 16-mer DNA duplex containing a site specific
intrastrand cisplatin 1,2-d(GpG) cross-link, reveals intercalation of a
phenylalanine side chain into the hydrophobic cleft created in the minor
groove across from the platinum adduct. Binding of HMG-domain proteins
in this manner shields Pt adducts from nucleotide excision repair. TATA
binding protein (TBP) similarly recognizes intrastrand cisplatin
1,2-d(GpG) cross-links by intercalation of phenylalanine side chains.
Both hSSRP1, the first protein identified to bind with specificity to
cisplatin-DNA adducts, and TBP are required for transcription. Cisplatin
disruption of transcription may be the key event in its anticancer
mechanism. The natural functions of HMG1 include facilitating the
binding of steroid hormone receptors, such as estrogen or progesterone
receptor (ER or PR), to their cognate DNA binding sites. HMG1 levels in
human cancer cells bearing the appropriate hormone receptor, ER or PR,
increase upon estrogen or progesterone treatment. In human MCF-7 breast
cancer cells, which have both ER and PR, HMG1 was elevated after
estrogen and progesterone treatment. Evsa-T is a breast cancer cell line
that has PR but not ER. Estrogen treatment had no effect on HMG1 levels
in Evsa-T cells. Progesterone doubled the HMG1 protein level in Evsa-T
cells. Elevated HMG1 expression levels parallel increased sensitivity
towards cisplatin. In MCF-7 cells, estrogen or progesterone treatment
increased cisplatin sensitivity about 2-fold, according to LC~50~
values. A combination of estrogen and progesterone increased cisplatin
sensitivity by a factor of 4; this additive effect suggests that these
two hormones up-regulate HMG1 independently. These findings form the
basis for a clinical trial to commence this year at the Dana Farber
Cancer Institute. This work was supported by the NCI.

Metal-Catalyzed Cleavage of Nucleic Acids

Cynthia J. Burrows, Ph.D., Department of Chemistry, University of Utah,
Salt Lake City, Utah, USA, 84112-0850.

The sugar, the phosphate and the base moieties constitute the three
chemical targets for metal-mediated reactions leading to scission of a
DNA or RNA strand. Certain metal complexes, particularly those of
lanthanides, can act as Lewis acids to facilitate phosphodiester
hydrolysis; this occurs most readily for RNA in which the 2\'-OH greatly
enhances hydrolysis via intramolecular transesterification. Catalysts
for efficient DNA hydrolysis have been a more difficult target, but some
success in now seen in this area. In contrast, there are now a large
number of redox-active transition metal complexes, particularly those
capable of forming free or metal-bound electron-deficient oxygen species
(metal-oxo, HO•, O~2~^--\ •^, etc.) that trigger DNA and RNA strand
scission following hydrogen atom abstraction from the ribose moiety.
Although metal complexes targeting phosphates or sugars typically have
little intrinsic sequence or structure selectivity because all
phosphates and all riboses roughly look alike, clever ligand design has
led to cleavage agents that act upon specific primary, secondary or
tertiary structures of nucleic acids. The third target--the heterocyclic
bases--will form the major focus of this presentation. Guanine in
particular presents a wealth of sites for metal binding and oxidation or
alkylation. In principle, any metal complex that is sufficiently
oxidizing to attack hydrogen atoms of the ribose moiety is also capable
of abstracting an electron from G. Base oxidation does not directly
yield strand scission, but rather creates a site that is sensitive to
cleavage using either chemical reagents (such as HO^--^ or piperidine)
or enzymes, principally those involved in DNA repair. Our laboratory has
investigated a series of nickel(II) complexes that operate almost
exclusively by one-electron oxidation of Gs. Ligand tuning provides
complexes capable of reacting with O~2~ in the presence of a sacrificial
reductant (usually sulfite) to generate Ni(III) species leading to
oxidative damage at G. With redox-active ligands, the role of Ni(III) is
to trigger formation of ligand radicals capable of generating covalent
adducts.

Applications of nickel complexes to biomedical research include their
use as (*i*) structural probes of DNA and RNA folding, (*ii*)
sequence-specific cleavage agents when tethered to DNA recognition
agents, (*iii*) site-specific tags of DNA or RNA allowing conjugation of
fluorescein, biotin or other molecular probes, and (*iv*) models of
DNA-based metal toxicity.

![](media/image2.wmf)

Leading references:

1\. C. J. Burrows and J. G. Muller, "Oxidative Nucleobase Modifications
Leading to Strand Scission," *Chem. Rev.* **1998**, *98*, 1109-1152.

2\. A. J. Stemmler and C. J. Burrows, "The Sal-XH Motif for
Metal-mediated Oxidative DNA-Peptide Cross-linking," *J. Am. Chem. Soc*.
**1999**, *121*, 6956-6957.

3\. S. E. Rokita and C. J. Burrows, "Probing Nucleic Acid Structure with
Nickel and Cobalt-based Reagents," *Current Protocols in Nucleic Acid
Chemistry*, **2000**, 2.4.1-2.4.7

**Selective Inhibition of Human α-Thrombin by Co(III) Schiff Base
Complexes**

Thomas J. Meade**,** Division of Biology and the Beckman Institute,
California Institute of Technology, Pasadena, California, USA, 91125.

The use of metals in medicine has grown impressively in recent years as
the result of a greatly advanced understanding of the structures of
biologically active metal complexes and metal-containing proteins. A
challenge for those in the inorganic and bioinorganic communities is the
preparation of novel inorganic therapeutic agents that can be
specifically coupled to a biologically active site by cooperative
redox-binding ligation. We report on the selective inhibition of the
serine protease human α-thrombin by Co(III) Schiff base complexes. These
complexes bind protein residues by ligand substitution at active sites
and on enzyme surfaces in a random fashion. In order to increase
inhibitor specificity and potency, a short peptide (-dFPR-) that is
known to have a high affinity for the human α-thrombin active site was
covalently attached to the Co(III) complex. This work demonstrates that
an active-site-directed peptide linked to a cobalt chelate can
selectively inhibit thrombin and provides a platform for new inorganic
drug candidates.

**Metal Complexes and Drug Transport**

David Piwnica-Worms, Program in Bioorganic Chemistry, Washington
University School of Medicine, St. Louis, Missouri, USA, 63110.

Resistance to chemotherapeutic agents remains one of the major obstacles
to successful systemic therapy of human cancer. The multidrug resistance
(*MDR1*) P-glycoprotein (Pgp) and the multidrug resistance-associated
protein (MRP), members of the ATP-binding-cassette transporter family,
are two of the best characterized of these resistance mechanisms. These
transporters are conventionally thought to contribute to multidrug
resistance by "exporting" drugs out of tumor cells in an
energy-dependent manner and are relevant to a wide range of human
cancers. Strategies designed to block expression or to circumvent this
form of drug resistance are being actively sought by many academic and
industrial laboratories in cancer research. To properly use these new
target-selective drugs, highly sensitive assays for direct detection and
functional characterization of the transport activity of Pgp and MRP *in
vivo* would be desirable. We have synthesized and validated a variety of
complexes incorporating gamma-emitting metal isotopes that are
transported by *MDR1* Pgp. These compounds include N~4~O~2~ Schiff-base
phenolic \[^68^Ga(III)\]-complexes,
hexakis(arylisonitrile)\[^99m^Tc(I)\]-complexes, and N~2~O~2~P~2~
\[^99m^Tc(I)\]-complexes as PET and SPECT imaging agents. We have
extensively characterized these complexes using baculoviral expression
of recombinant human *MDR1* in host cells, human tumor xenografts in
nude mice models, and *mdr1a/1b*(-/-) knockout mice. In addition, two
commercial radiopharmaceuticals, \[^99m^Tc\]Sestamibi and
\[^99m^Tc\]Tetrofosmin, have been validated as imaging probes of Pgp
transport activity in patients and clinical studies are underway to
functionally detect MDR in patients with advanced breast cancer**.**

The favorable cell membrane permeability properties of Schiff-base and
amine phenolate metal complexes also have been exploited to generate
novel antimalarials. These scaffolds are amenable to accommodating a
variety of metals, including Al(III), Ga(III) and In(III), in addition
to biocompatible metals relevant to malaria-host interactions such as
Fe(III). Inhibiting both chloroquine-resistant and -sensitive strains,
efficacy of these metal complexes correlates with their ability to
inhibit heme polymerization, the same vital target as chloroquine,
within the food vacuole of the causative organism, *P. falciparum*. An
unusual selectivity profile has been discovered with complexes of the
3-MeO substituted ligand. This compound, equipotent as the Ga(III) or
Fe(III) complex, is cytotoxic with an IC~50~ of \<0.5 M, but
selectively traverses the chloroquine resistance mechanism. Curiously,
in a genetic cross of 21 independent recombinant progeny, susceptibility
of this complex maps in perfect linkage with the chloroquine resistance
phenotype suggesting that a locus for susceptibility to this compound is
located on the same 36 kilobase segment of chromosome 7 previously
identified as the chloroquine-resistance determinant. This metal complex
offers an interesting template for the development of novel
antimalarials that selectively target chloroquine resistance and in
addition, may be useful as a probe of chloroquine resistance mechanisms
in *P. falciparum.*

**Metal Complexes as Receptor Ligands**

Shubh Sharma, Palatin Technologies Inc., 175 May Street, Suite 500,
Edison, New Jersey, USA, 08837.

Peptides constitute an excellent class of molecules for rapid drug
discovery and lead optimization. This is promised by their high degree
of structural diversity and conformational states. However, this very
floppy structure eludes mapping a pharmacophore model for a biological
target that is crucial to rapid translation of peptidic leads into
peptidomimetics and small organic molecules with drug-like
characteristics. Even the cyclized peptides and other conformationally
restricted peptides and peptido-mimetics developed by the use of
designer amino acids present these difficulties due to existence of
multiple conformational states within these molecules. These
difficulties are best exemplified by the fact that majority of attempts
to convert peptide based agonists into small organic molecules usually
result in the development of antagonists.

We are developing highly rigid and structurally well defined scaffolds
obtained by complexing a metal-ion to a pre-designed linear peptide for
their use in the process of drug development. These scaffolds are then
decorated with suitable functional groups to induce biological affinity
and specificity for a given biological receptor. The rigid structure of
these complexes is predictable due to well defined geometry of the
metal-ion co-ordination sphere. Our approach towards development of
receptor specific Re\[V\]O complexed metallo-peptides will be presented.
In particular, development of potent and receptor selective
metallopeptide ligands for melanocortin receptors will be discussed

**Metalloenzyme Drug Development Targets at Merck**

John W. Kozarich, Merck Research Laboratories, PO Box 2000, Rahway, New
Jersey, USA, 07065-0900.

Metalloproteases and peptidases constitute a diverse family of enzymes
many of which have therapeutic potential. Two metallopeptidases of
potential importance as antimicrobial targets, carbapenemase and peptide
deformylase will be discussed. The efforts at Merck to design potent
inhibitors of these enzymes that rely on coordination to the
metal-containing catalytic center will be presented. In addition, SAR,
high resolution X-ray structures of complexes and in vitro and in vivo
efficacy data will also be presented.

**Nitric Oxide Synthase**

Thomas L. Poulos, C.S. Raman, and Huiying Li, Department of Molecular
Biology and Biochemistry, University of California, Irvine, California,
USA, 92697-3900.

Nitric oxide synthase (NOS) catalyzes the conversion of arginine to
citrulline and nitric oxide. The reaction proceeds in two steps. The
first step is a classic P450-like monooxygenation where one O~2~ derived
O atom is added to the substrate in a reaction requiring two electrons.
The second step is more unique to NOS, since only one electron and O~2~
are required. NOS requires the essential co-factor tetrahydrobiopterin
(H~4~B) which now is thought to be a source of electrons during the O~2~
activation part of the NOS catalytic cycle. NOS is a homodimeric protein
consisting of a heme, FMN, and FAD domains. The flow of electrons is
from NADPH-to-FAD-to-FMN-to-heme. There are three human NOS isoforms:
eNOS (endothelial NOS, cardiovascular system, iNOS (inducible NOS,
immune system), and nNOS (neuronal system). Both eNOS and nNOS are
regulated by calmodulin, and the NO produced by these isoforms is
targeted to guanylate cyclase (GC). The binding of NO to GC activates GC
leading to production of the ultimate signaling molecule, cGMP. iNOS has
calmodulin bound as permanent subunit and does not operate via GC but
instead, iNOS produced NO is used as a cytotoxic molecule to help ward
off infection. There is considerable interest in developing
isoform-selective inhibitors. For example, one would like to block the
cytoxic effects of NO produced by iNOS or ischemic injury due, in part,
to NO produced by nNOS while leaving eNOS alone owing to its critical
role in maintaining vascular tone. Toward this end we have solved the
crystal structure of the heme domain for all three isoforms. eNOS
crystals diffract best which has enabled us to solve the structure of
several eNOS-inhibitor complexes. Some of these have provided important
insights into the catalytic mechanism as well as what features of the
substrate are most critical for binding and activity. In some cases
there have been surprises, where a compound thought to be targeted to
the active site also is an antagonist of H~4~B binding. It has become
clear that using structure-based drug design to develop
isoform-selective inhibitors will be a challenging problem since the
structure of the three isoforms are so similar including active site
details. Therefore, it is likely that selective inhibitors may need to
be targeted to regions of the protein outside of the active site where
sequence variations are larger. Some of the eNOS structures solved
provide hints as to how this might be accomplished. Supported by NIH
Grant GM57353H 4 B

**Molecular Modeling Of Metalloenzymes: Current Status And Future
Prospects**

Kenneth M. Merz Jr., Department of Chemistry, The Pennsylvania State
University, University Park, Pennsylvania, USA, 16802.

In this presentation we will give a brief overview of how molecular
modeling has been accurately and fruitfully applied to the study of
metalloenzymes. Using zinc metalloenzymes as our paradigm, we will trace
the use of molecular mechanics (MM), combined quantum mechanics(QM)/MM
and fully QM studies of zinc containing enzymes. Particular focus will
be given to the electrostatic representation of the metal containing
active site in metalloenzymes using these diverse methodologies.
Finally, the future prospects and impact of using ever more
sophisticated modeling tools to study metalloenzymes will be discussed.

**Modeling Matrix Metalloproteases: A Case Study**

Benjamin Burke, Agouron Pharmaceuticals, Inc., San Diego, California,
USA, 92121-1111.

Matrix metalloproteases are a family of enzymes that play important
roles in controlling the integrity of extracellular matrix. The
therapeutic applications proposed for inhibitors of this family include
cancer, arthritis and ophthalmological diseases. The active site of this
family of enzymes contains a zinc critical for activity. This zinc is
liganded by inhibitors containing a variety of chelating groups. The
manner in which the different ligands interact with the zinc will be
discussed. We have developed a molecular model of the zinc cluster and
have used it in studies to predict ligand affinity within certain
chelating group classes. Our model is described along with the results
of the study.

Fundamentals of Receptor-Based Metalloradiopharmaceuticals

Shuang Liu, Medical Imaging Division, DuPont Pharmaceuticals Company,
North Billerica, Massachusetts, USA, 01862.

Development of a receptor-based target-specific radiopharmaceutical is a
long and complicated process, and requires a good understanding of
fundamentals in biology, chemistry and nuclear medicine. Significant
progress has been made for the last several years in the development of
peptide target-specific radiopharmaceuticals. ^99m^Tc-labeled small
peptides have become a class of imaging agents for the diagnosis of
various diseases while ^90^Y-labeled somatostatin analogs are under
investigation for tumor radiotherapy. This talk will focus on some
fundamental aspects in the design and development of target-specific
radiopharmaceuticals based on small peptides, the technetium chemistry,
technetium cores and bifuctional coupling agents, quality control and
characterization of ^99m^Tc-labeled small peptides. It will also present
some of our recent results on the isomerism and solution dynamics of
^90^Y-labeled DTPA- and DOTA-biomolecule conjugates.

**Radiolabeled Somatostatin Analogs for Targeted Radiotherapy of
Cancer**

Carolyn J. Anderson, Washington University School of Medicine, St.
Louis, Missouri, USA, 63110.

Targeted radiotherapy is the administration of a radiolabeled molecule
designed to deliver a therapeutic dose of radiation to malignant tumors
with high specificity, while maintaining low accumulation in non-target
tissues. Radionuclides used to label radiopharmaceuticals for cancer
therapy generally decay by particle emission, i.e. α, β^-^, β^+^ or
Auger electrons. Metal radionuclides for labeling therapeutic
radiopharmaceuticals include ^90^Y, ^111^In, ^177^Lu, ^67^Cu and ^64^Cu.
Analogs of the hormone somatostatin have been labeled with metal
radionuclides, and they target somatostatin-receptor-positive tumors as
both diagnostic and targeted radiotherapy agents.
Indium-111-DTPA-octreotide and ^90^Y-DOTA-Tyr^3^-octreotide are
currently in clinical trials as targeted radiotherapy agents for
patients with neuroendocrine tumors at various institutions in the U.S.
and Europe.

Copper-64 (half-life = 12.7 h; 17.4% β^+^; 39% β^−^) has applications in
diagnostic imaging with positron emission tomography (PET) and targeted
radiotherapy. At Washington University School of Medicine, we developed
several ^64^Cu-labeled somatostatin analogs and have demonstrated their
potential as PET imaging and targeted radiotherapy agents. A clinical
PET imaging trial showed that ^64^Cu-TETA-octreotide imaged
neuroendocrine tumors in patients as effectively as
^111^In-DTPA-octreotide (a FDA approved imaging agent) and conventional
gamma scintigraphy. In two patients, more tumors were visualized with
^64^Cu-TETA-octreotide. Pre-clinical targeted radiotherapy studies have
been carried out with ^64^Cu-TETA-Tyr^3^-octreotate in a tumor-bearing
rat model, and complete tumor regressions occurred in all treated rats.
The therapeutic effectiveness of ^64^Cu-labeled somatostatin analogs may
be related to the fact that in cells treated with
^64^Cu-TETA-octreotide, ^64^Cu was found to localize in the cell
nucleus, which may increase the probability of tumor cell death. Taken
together, these data suggest that ^64^Cu-labeled somatostatin analogs
may be effective as targeted radiotherapy agents in patients with
somatostatin-receptor-positive tumors.

**Biophysical Tuning and Targeting of Gadolinium(III) Chelates for MRI**

Randall B. Lauffer, EPIX Medical, Inc., Cambridge, Massachusetts, USA,
02142.

The development of new magnetic resonance imaging (MRI) contrast agents
is an active area related to bioinorganic chemistry. Most of the current
emphasis is in the design of new gadolinium(III) chelates that localize
in a particular area of the body and cause large enhancements in the
1/T1 relaxation rate of water protons. In addition to the synthesis of
new chelates that bind to protein targets, active areas of investigation
include the dependence of relaxivity on the rigidity of binding as well
as the inner sphere water residence time and electron spin relaxation
behavior. The development and properties of AngioMARK (MS-325), an
albumin-targeted agent in advanced clinical trials for blood vessel
imaging, will serve to illustrate these areas. In addition, a
fibrin-targeted Gd-based agent is also under development which would
allow the direct detection of blood clots as a bright spot on MR images

# Metallotexaphyrins: New Drugs with Diverse Applications in Cancer Treatment

Richard A. Miller, Darren Magda and Jonathan L. Sessler, Pharmacyclics,
Inc., Sunnyvale, California, and the Dept. of Chemistry and
Biochemistry, University of Texas, Austin, Texas.

Texaphyrins are porphyrin-like macrocycles which form highly stable
complexes with large metal cations. These molecules possess several
interesting properties that led to their consideration for use in cancer
therapy. Texaphyrins have a low energy absorption peak at 732 nm and are
electron affinic or easily reduced with a reduction potential of 0.08V
(NHE). These molecules localize in tumors, similar to naturally
occurring porphyrins. Two such metallotexaphyrins, motexafin gadolinium
and motexafin lutetium, are currently in advanced clinical trials for
cancer treatment.

Compounds that display an affinity for electrons can potentiate the
biological effects of ionizing radiation and are known as radiation
sensitizers. Some of these agents, like oxygen, can react directly with
cellular macromolecules to cause damage. Unlike these agents, motexafin
gadolinium reacts with cellular metabolites having a high reduction
potential, e.g., NADPH, reduced glutathione or ascorbate. This leads to
the localized production of reactive oxygen species. When tested in
several animal tumor model systems, motexafin gadolinium produces
radiation enhancement determined by tumor growth delay. Motexafin
gadolinium has completed phase I and phase II clinical trials as a
radiation enhancer. The dose limiting toxicity in these studies was
hepatocellular damage. Comparison to historical data suggested a
favorable effect on overall survival in patients with brain metastases
receiving whole brain radiation therapy. This drug is now in a
multicenter prospective randomized trial in patients with metastatic
cancer to the brain. The drug is administered IV prior to each fraction
of radiation therapy. The co-primary end-points of this study are
survival or time to neurologic progression. MRI scanning has been used
to establish tumor selectivity, based on the paramagnetic properties of
the molecule.

Motexafin lutetium is in a phase II trial for the photodynamic therapy
(PDT) of recurrent cutaneous breast cancer and a phase I trial for PDT
of locally recurrent prostate cancer. This drug appears to have a dual
mechanism of action: It produces singlet oxygen following activation
with 732 nm light and depletes intracellular reducing metabolites in the
absence of light. Its rapid plasma clearance (plasma half life, 3 hrs.)
and activation by tissue penetrating far red light are important
features, which may reduce toxicity and increase efficacy. This drug is
also being tested in phase II trials in patients with age related
macular degeneration; a leading cause of blindness, and as an
endovascular therapy for atherosclerosis.

Motexafin gadolinium and motexafin lutetium provide a new class of drugs
with diverse applications. Their favorable tissue biolocalization,
chemical features and novel mechanisms of action should continue to
offer encouraging new approaches to cancer therapy.

# Intracellular Trafficking Pathways: Inorganic Cell Biology of Copper and Zinc

# Thomas V. O\'Halloran, Department of Chemistry, Northwestern University, Evanston, Illinois, USA, 60208-3113.

How do intracellular proteins acquire essential cofactors like copper or
zinc? It has long been thought that metalloproteins are highly specific
chelators that select the appropriate metal ions from the cytoplasm of
the cell. Recent studies indicate that the \'free\' copper
concentrations within the cell are too low to allow an apoprotein to
acquire copper without accessory factors. It is now clear that
diffusible cytoplasmic proteins, the metallochaperones, protect and
guide the copper ions to a particular intracellular enzyme.

A prototypical member of the growing family of these metallochaperones
is Atx1, a protein involved in copper trafficking in yeast and humans.
Physical, structural and mechanistic studies of copper chaperone
proteins reveal novel coordination environments. Structural indicates
that the metal binding loop in Atx1 is conformationally flexible and is
consistent with EXAFS and NMR studies indicating that the protein
readily allows formation of both a two and a three coordinate geometry
at copper. This chemistry is a basis for facile metal transfer to and
from the target proteins, including the N-terminal CxxC domains of the
Wilson and Menkes disease proteins. Atx1-like domains have also been
observed in the copper chaperones for superoxide dismutase (CCS);
however, cysteine residues from other domains play a critical role in
copper binding. The results for both families of copper chaperone reveal
a series of allosteric 'capture and release' steps in the metal transfer
mechanism.

Cells thus rigorously control the activity of redox active copper
species, but far less is known concerning the more abundant and less
toxic complex ions of zinc. To address this issue, new compounds that
can chelate zinc inside or outside of the cell are being designed with a
variety of zinc affinities. Knowledge of the intracellular
thermodynamics and kinetics of both zinc and copper metabolism may be
useful in the design of compounds that alter intracellular metal ion
availability. This in turn may be useful in controlling a wide range of
biological phenomenon including proliferation of cancer cells, disorders
of metal metabolism and metal induced neurotoxicity during ischemia.
(Supported by NIGMS and NIDDK)

**Combinatorial RNA Regulation Of Bio-Iron And New Drug Targets**

Elizabeth C. Theil, Children\'s Hospital Oakland Research Institute
(CHORI), Oakland, California, USA, 94609-1673

Iron and oxygen chemistry can create rust and active oxygen species
(ROS). Biology uses many molecular strategies to manage and use iron and
oxygen. Regulation of iron metabolism (Bioiron) uses both DNA and RNA as
targets, which contrasts with oxygen metabolism where DNA is the target.
Recent recognition of the co-regulation of mRNA for one step in oxygen
metabolism (m-aconitase in the TCA cycle) and the mRNAs for bioiron
suggests that the apparent difference may be fleeting.

Bioiron has three components: 1-*Iron trafficking*
\[extracellular=transferrin, lactoferrin; transmembrane=transferrin
receptor (TfR), DMT-1 and IREG1/ferroportin1 and intracellular iron
transport\] 2-*Iron accumulation* \[concentration and storage by
ferritin\]; 3-*Iron cofactors*: (globins, cytochromes, oxygenases).
Classical DNA transcription targets, encoding iron trafficking, iron
accumulation and iron cofactor proteins, respond to environmental iron
signals. Unique mRNA (IRE) and binding (IRP) targets, encoding iron
trafficking, iron accumulation and iron cofactor proteins, respond
differentially to environmental iron signals by combinatiorial use of
the mRNA and binding protein isoforms. Combinatorial mRNA regulation
together with classical DNA regulation of Bioiron emphasizes the crucial
role of iron in biology and the ferrocentricity of life.

Potential drug targets to regulate Bioiron are the IRE structures in
mRNA, as well as the protein channels in ferritin, for treating iron
overload in hemochromatosis, sickle cell disease and thalassemia. The
mRNA targets of Bioiron also model mRNA structures in oncogenes (c-fos,
c-myc) and viruses (HIV). Selective targeting of iron chelators to
ferritin channels and shape-specific metal complexes to mRNA isoforms
are goals for new drugs of the new century.

# Metal Chelation Therapy

K. N. Raymond^1^, J. Xu^1^, K. M. Clarke^1^, B. O' Sullivan^1^, R. A.
Yokel^2^, A. M. Fredenburg^2^, P.W. Durbin^3^, B. Kullgren^3^, and G.
Watson^4^

^1^College of Chemistry, Univ. of California, Berkeley, California;
^2^College of Pharmacy, Univ. of Kentucky Medical Center, Lexington,
Kentucky; ^3^Lawrence Berkeley National Laboratory, Berkeley,
California; ^4^Children's Hospital of Oakland Research Institute,
Oakland, California.

The shortcomings of current chelation therapy have stimulated efforts to
develop orally active Fe chelators\[1\]. Bidentate hydroxypyridinones,
particularly L1 (deferiprone; 1,2-dimethyl-3-hydroxypyrid-4-one) \[2\],
at high concentration can effectively complex and decorporate trivalent
iron. However, toxicity problems of L1 have made its use controversial.
We contend that any bi- or tridentate ligand will be ineffective at low,
safe dose levels. We report two studies to test the potential of
multidentate 3,2-hydroxypyridinone-based ligands as therapeutic iron
chelators. In the first study\[3\], urinary and biliary Fe excretion
were determined in Fe-loaded rats before and after administration of
bidentate Me-3,2-HOPO-propylamide \[Pr-(Me-3,2-HOPO)\] or its
hexadentate analogue, TREN-(Me-3,2-HOPO). Bidentate Pr-(Me-3,2-HOPO)
slightly increased urinary and biliary Fe output in Fe-loaded rats after
oral (90 or 270 µmol/kg po) or intravenous administration (90 µmol/kg
iv), but chelation efficiency did not exceed 1%. Hexadentate
TREN-(Me-3,2-HOPO) increased urinary Fe excretion slightly and increased
biliary Fe excretion markedly, achieving overall efficiencies of 3 to
14% after oral (30 or 90 µmol/kg) or iv administration (30 µmol/kg),
respectively. In ligand-treated Fe-loaded rats, more than 90% of the
excreted Fe was in the bile. Oral TREN-(Me-3,2-HOPO), given to control
rats, did not significantly change Fe output, indicating little iron
depletion in the absence of Fe overload.

In the second study\[4\], the ability of tetradentate 5LIO-Me-3,2-HOPO
to decrease the liver, heart, spleen and kidney iron levels in
iron-loaded mice was compared to that of desferrioxamine B. Fe-loaded
mice were treated for one week with daily injections of chelator (500
μmol/kg ip) or saline control. 5LIO-Me-3,2-HOPO showed the same
effectiveness as desferrioxamine B, decreasing the liver iron load by
\~25% in the treated mice relative to the untreated mice. Neither
chelator had a significant effect on the heart, spleen, or kidney iron
levels. The results from these two studies indicate that multidentate
3,2-hydroxypyridinone ligands are promising therapeutic iron chelators.
The results from the first study also support the general hypothesis
that hexadentate or tetradentate hydroxypyridinone chelators are more
effective than their bidentate analogs at low, and presumably safer,
concentrations.

Supported by NIH Grant DK32999 and DK 57814 and the Office of the Vice
Chancellor for Research and Graduate Studies, University of Kentucky
Medical Center.

1.*The Development of Iron Chelators for Clinical Use*; Bergeron, R. J.;
Brittenham, G. M., Eds.; CRCPress;Boca Raton, **1994**; B. O'Sullivan;
J. Xu; K. N. Raymond, "New Multidentate Chelators for Iron" in *Iron
Chelators: New Development Strategies*; Bergeron, R. J.; Badman, D. G.;
Brittenham, G. M., Eds.; Saratoga Publishing Group, in press.

2.Hider, R. C.; Singh, S.; Porter, J. B.; Huehns, E. R., "The
Development of Hydroxypyridin-4-ones as Orally Active Iron Chelators;"
*Ann. NY Acad. Sci*. **1990**, *612*, 327-338.

3.Yokel, R. A.; Fredenburg, A. M.; Durbin, P. W.; Kullgren, B.; Xu, J.;
Raymond, K. N. *J. Pharm. Sci*., in press.

4.Clarke, K. M.; Xu, J.; Watson, G.; Raymond, K. N., ongoing research at
CHORI.

**Chromium as a Dietary Supplement**

Richard A. Anderson, Nutrient Requirements and Functions Laboratory,
USDA Beltsville Human Nutrition Research Center, Beltsville, Maryland,
USA, 20705.

Chromium is an essential element required for normal carbohydrate and
lipid metabolism. Normal dietary Cr intake for humans and farm animals
is often sub optimal. Insufficient dietary intake of chromium leads to
increases in risk factors associated with diabetes and cardiovascular
diseases including elevated circulating insulin, glucose, triglycerides,
total cholesterol, reduced HDL-cholesterol, and impaired immune
function. Chromium was shown to be an essential element in humans during
the seventies when a patient on total parenteral nutrition developed
severe signs of diabetes including weight loss, glucose intolerance and
peripheral neuropathy that were refractory to insulin. Since
conventional treatments for diabetes, including 200 units of insulin per
day, were unsuccessful, the patient was given supplemental chromium
based on previous animal studies and preliminary human studies.
Following two weeks of supplemental chromium, signs and symptoms of
diabetes were reversed and exogenous insulin requirements dropped from
200 units per day to zero. Within the past five years, improved chromium
nutrition has been shown to improve glucose intolerance and type 1, type
2, gestational and steroid-induced diabetes. Chromium requirements are
related to degree of glucose intolerance and diabetes. Glucose tolerance
of subjects with mild glucose intolerance declines when consuming diets
containing less than 20 µg of Cr per day (normal daily dietary Cr intake
is 25 to 40 µg) for five weeks while glucose tolerance of subjects with
near optimal glucose tolerance is not altered by these low Cr intakes.
People with diabetes also have a higher requirement for Cr. Chromium
supplementation with 200 µg of Cr per day to people with mild glucose
intolerance results in significant improvements while blood glucose of
people with diabetes often does not respond. However, daily Cr
supplementation of 400 µg or more results in significant improvements in
many people with diabetes. Chromium improves insulin function by
increasing insulin binding to cells, insulin receptor number, and
phosphorylation of the insulin receptor leading to increased insulin
sensitivity. Chromium is one of the least toxic nutrients and there have
been no documented negative effects of supplemental chromium at intakes
up to 1000 µg per day. While the toxic effects of chromium are limited
to a small percentage of the population primarily exposed to chromium in
occupational settings, the effects of marginal chromium nutrition are
widespread and may affect a large percentage of the general population.
In summary, dietary Cr intake is often sub optimal and improved chromium
nutrition has been shown to play a role in the prevention and
alleviation of risk factors associated with diabetes and cardiovascular
diseases.

**Mechanisms Of Metal Toxicity**

Max Costa1, Konstantin Salnikow1, Wu Peng1, Jessica Sutherland1,
Moon-shong Tang1, Chuanshu Huang2, and Xianglin Shi2

1Department of Environmental Medicine, New York University School of
Medicine, New York, New York, 2National Institute of Occupational Safety
and Health, Morgantown, West Virginia.

To illustrate the diversity of metal actions in cells, I will discuss
two very different metals, Cr(VI) and Ni. Cr(VI) enters cells very
efficiently by an anion transport system and is subsequently reduced
inside the cells to Cr(III) which binds to proteins and DNA. Its binding
to DNA creates adducts involving the six coordination sites of Cr(III)
with the phosphate backbone of DNA, N-7 of guanine, and amino acids,
such as cysteine, glutathione, and larger peptides and protein
molecules. These ternary DNA complexes are very stable but can be
dissociated with chelators, such as EDTA, and this fortuitously allows
for specificity in their detection and mapping. We have recently
utilized UvrABC bacterial repair enzymes and ligation-mediated PCR to
detect and map Cr DNA adducts at the nucleotide level in the *p53* gene
in human cells. Ni, in contrast to Cr(VI), is quite different in that
the soluble forms do not as readily enter cells but the insoluble forms,
such as Ni3S2, NiS, and NiO are phagocytized by cells and yield high
levels of solubilized Ni in the cell. These forms of Ni compounds are
very carcinogenic and interact with chromatin. In particular, in
heterochromatin, Ni substitutes for Mg2+ on the phosphate backbone of
DNA and increases chromatin condensation triggering *de novo* DNA
methylation which may decrease the expression of tumor suppressor genes.
In yeast, Ni compounds inhibit histone H4 acetylation which down
regulates gene transcription. Additionally, soluble as well as insoluble
forms of Ni, activate specific signaling cascades in cells by several
mechanisms at nontoxic doses. Ni activates HIF-1α (hypoxia inducible
factor), *ATF1*, and *p53* by increasing the protein stability of these
very important transcription factors. Ni also activates Ca2+ signaling
by increasing expression of Ca-regulated genes, such as *Cap43* and
Ca-dependent transcription factors such as NFAT. These effects are very
specific because Ni does not alter transcription of genes containing
RARE, GRE, or CRE sequences in their promoters or, *p53*, and *ATF1*.

**Vanadium And Diabetes**

Chris Orvig, Medicinal Inorganic Chemistry Group, Department of
Chemistry and Faculty of Pharmaceutical Sciences, University of British
Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada.

Vanadium has long been of interest to bioinorganic chemists and
enzymologists. More recently, this element has shown potential for a
number of therapeutic applications, most of which have arisen as a
byproduct of vanadate's role as a biological probe of phosphate
utilization, despite the on-going controversy concerning the
essentiality of vanadium.

A number of vanadium compounds have been reported to have
insulin-enhancing properties, most notably when administered orally (a
route via which insulin is not active). Still, gastrointestinal
absorption of vanadium is usually poor and depends on the chemical
nature, solubility, and speciation of the specific metal ion complex.
Little is known about the coordination properties of orally administered
vanadium compounds *in vivo*, about the factors required to deliver
vanadium to its ultimate site of action, or indeed where that site of
action is.

The orally effective therapeutic agent bis(maltolato)oxovanadium(IV)
(**BMOV**) is a potent insulin-enhancing agent for the treatment of
STZ-diabetic rats. BMOV and its analogues have considerable reaction
chemistry which has direct relevance to insulin-mimesis. One analogue
has completed phase I clinical trials in healthy subjects and will soon
begin phase II.

The preparations, redox chemistry, reaction chemistry and structures of
several of these compounds will be presented, along with pertinent EPR,
51V NMR, ESEEM, and 48V biodistribution data, as well as a model for the
uptake and distribution of vanadium.

**Computer-Aided Design Of Selective Synthetic Superoxide Dismutase
Enzyme Mimetics**

Dennis P. Riley, MetaPhore Pharmaceuticals, Inc., St. Louis, Missouri,
USA, 63114.

Mn(II) complexes of 1,4,7,10,13-pentaazacyclopentadecane ligands are SOD
catalysts (*JACS, 116,* 387 (1994)) with a unique selectivity for
superoxide (no reaction with O~2~, NO**^.^**, H~2~O~2~, or OONO^-^). To
optimize this class of complexes for high SOD catalytic activity and
high chemical and metabolic stability\--key features for a drug, we
studied the effect that C-substituents on the ligand exert on SOD
activity and stability. The results show that activity responds in an
unpredictable manner, while increasing the number of substituents
increases the stability of the complexes. Subsequent mechanistic studies
(*JACS, 119,* 995 (1997)) revealed that these catalysts function via a
catalytic cycle in which oxidation of Mn(II) is rate-determining. The
major path for activity arises from an "outer-sphere" oxidation of the
Mn(II)(L) complex via a H+-coupled electron transfer from a water bound
on the Mn(II)(OH~2~) center to HO~2~**^.^** generating H~2~O~2~ and
Mn(III)(OH), which is rapidly (diffusion-controlled) reduced to Mn(II)
generating O~2~. This path necessitates that the Mn(II) center have a
geometry similar to the oxidized Mn(III) product (Marcus-Hush Theory);
thus, accommodating the fast rates we observe for this process (\~ 1 x
10^+10^ M^-1^s^-1^). With this mechanistic insight, it was possible to
utilize molecular mechanics (MM) calculations to probe how ligand
substituents influence relative energies of their Mn(II) and Mn(III)
complexes, and thus alter the geometry of the Mn(II) complexes. The
ability of the ligands to fold about Mn(II) ion adopting a 6-coordinate
pseudo-O~h~ geometry-as required by Mn(III)- correlates with the rate
constants for the electron transfer process; i.e., ∆E between the lowest
energy Mn(II) folded structure and the corresponding Mn^+3^ structure
correlate with activity. Mechanistic details and results of MM
calculations are presented for several Mn^II,III^(L) complexes. This
design paradigm has been utilized to develop active, stable and
selective SOD mimetics of the M40403 class (***Science**, 286,* 304
(1999).

**Polyoxometalate Nanocluster HIV-1 Protease Inhibitors: A New Mode of
Protease Inhibition**

Craig L. Hill, Deborah A. Judd, James H. Nettles, Neysa Nevins, and
James P. Snyder, Department of Chemistry, Emory University, Atlanta,
Georgia, 30322; Raymond F. Schinazi, Emory University School of
Medicine; Jordan Tang Jacques Ermolieff, University of Oklahoma Health
Sciences Center.

Evaluation of a library of polyoxometalates (POMs) identified the
\"cap\" and \"belt\" isomers of the ellipsoidal POMs of formula
P2NbW17O62^7-^ (K7 salt) and the corresponding peroxoniobium POMs as
minimally toxic (IC50 values: 50 to \>100 M in PBM cells) broad
spectrum antiviral agents in cell culture (e.g. EC50 vs HIV-1 in PBM
cells: 0.17-0.83 M), that also selectively inhibit purified HIV-1
protease (HIV-1P) at sub-micromolar concentrations. Thus, theoretical,
binding and kinetics studies of the POM/HIV-1P interaction(s) were
conducted. The results from all 3 studies are in remarkable agreement
with one another and indicate that these POMs function not by binding to
the active site of HIV-1P, the mode of inhibition of all other HIV-1P
protease inhibitors, but by binding to a cationic pocket on the
\"hinge\" region of the flaps covering the active site (2 POMs and
cationic pockets per active homodimer of HIV-1P). The affinities (K~i~
values) from enzyme inhibition kinetics are \~1 nM in 0.1 M NaCl and
inhibition is non-competitive (kcat but not Km is affected by the POM
concentration). The status of POMs as antiviral agents and in new
applications (e.g. antimicrobial and catalytically active hygenic
surfaces, etc.) will be summarized.

**NCI Developmental Therapeutics Program Experience**

Jill Johnson, Developmental Therapeutics Program, Division of Cancer
Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland,
USA, 20892-7448.

The Developmental Therapeutics Program (DTP), in existence since 1955,
functions as the preclinical investigational arm of the Division of
Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI).
In this capacity the DTP has utilized a variety of empirical *in vitro*
and *in vivo* assays to select, from 10,000 or more compounds submitted
for evaluation each year, a small number of candidates per year for
anti-cancer or anti-HIV clinical development. DTP has evaluated
approximately 550,000 potential chemotherapeutic agents, 15,000 of which
have contained metals. Eleven metal-containing compounds been selected
over the years for presentation as potential anti-cancer or anti-HIV
clinical candidates, with three of these presentations resulting in
INDs. A review of the experience of the DTP in the preclinical
evaluation of metal containing compounds will be presented.

# Principles of Medicinal Chemistry for Inorganics.

Nicholas P. Farrell, Department of Chemistry, Virginia Commonwealth
University, Richmond, Virginia, USA, 23284-2006.

Development of small molecules as therapeutic and imaging agents
requires not only an understanding of their effects on target
biomolecular structure (how the drug works) but also appreciation of the
metabolism and pharmacokinetics involved (why the compound is a drug).
Successful medicinal inorganic chemistry will intersect synthetic,
bioinorganic and medicinal chemistry. Medicinal inorganic chemistry must
also situate itself within the current concepts of drug discovery. This
contribution will summarize some of these principles using as examples
the work in my laboratory on development of novel platinum-containing
anticancer agents, which act in ways complementary to the currently used
clinical agents.

Supported by NIH and American Cancer Society.

**The US Drug Approval Process - Challenges for Metallopharmaceuticals**

David A. Place, Center for Drug Evaluation Research, Food and Drug
Administration, Rockville, Maryland, USA, 20857.

This presentation will provide to developers of metallopharmaceuticals
information about special chemistry and regulatory issues that need to
be addressed in completing an FDA drug application. Among the issues to
be discussed:

1.  Unique considerations in characterizing metallopharmaceuticals;

2.  Specific technologies for characterizing metallopharmaceuticals;

3.  Differences in characterizing inorganic ions vs. coordination
    complexes;

4.  Pharm/tox and clinical relevance of metallochemistry issues;

5.  Overview of the FDA application process for developing a drug in the
    US.

**The Bicyclam Story: From Metal Complexes to Ligands and Back to Metal
Complexes**

Michael J. Abrams, Ph.D., AnorMed, Inc., Langley, British Columbia,
Canada, V2Y 1N5.

The anti-HIV activity of bicyclams such as AMD-3100 (figure 1) was
identified in a program to screen metal complexes and chelators for
anti-viral activity. We have recently reported that bis-azamacrocycles
such as AMD3100 and certain of their bis-transition metal complexes,
inhibit HIV replication by binding to the chemokine receptor CXCR4, the
co-receptor used by T-tropic (T-cell tropic) (X4) HIV viruses for
membrane fusion and entry of the virus into cells of the immune system
*(J. Med. Chem.* 1995, *38*, 366-378; *Molecular Pharmacology* 1999,
*55*, 67-73; *J. Med. Chem.* 1999, *42*, 3971-3981; and references
therein).

> ![](media/image3.wmf)
>
> Figure 1: Structure of AMD3100.

In anti-viral activity assays in MT-4 cells, the prototype bicyclam,
AMD3100 exhibits an IC~50~ against HIV-1 (NL4.3, III~B~) and HIV-2 (ROD)
replication of 1-10 nM, which is at least 100,000 fold lower than the
cytotoxic concentration.

In this lecture, the discovery, SAR and the affect of metal ion
coordination on the biological properties of the bicylam class will be
discussed.

SPEAKER BIOSKETCHES

(IN ORDER OF PRESENTATION)

**Stephen J. Lippard, Ph.D., Arthur Amos Noyes Professor & Chair,
Department of Chemistry, Massachusetts Institute of Technology**

B.A. in chemistry, 1962, Haverford College, Haverford, Pennsylvania;
Ph.D. in chemistry, 1965, Massachusetts Institute of Technology;
postdoctoral, Massachusetts Institute of Technology. Assistant Professor
(1966-1969), Associate Professor (1972-1982), Professor (1972-1982),
Department of Chemistry, Columbia University; Professor of Chemistry
(1983-1989), Arthur Amos Noyes Professor of Chemistry (1989-present),
Head Department of Chemistry (1995-present), Massachusetts Institute of
Technology. Sabbaticals: University of Göteborg, Sweden with B. G.
Malmström, 1972; MRC Laboratory of Molecular Biology, Cambridge, England
with A. Klug, 1979;Anorganisch-Chemisches Institut der Technischen
Universität München, Garching, Federal Republic of Germany with W.
Herrmann, 1988; Department of Pharmacology, UCSD, San Diego, CA with R.
Tsien, 1998.

Honors: Scientific Member, Max-Planck-Gesellschaft; Elected Honorary
Member, Italian Chemical, Society; Chair, Gordon Research Conference on
Metals in Biology; Honorary D. Sc. Degree, Texas A&M University; William
H. Nichols Medal, New York Section of ACS; ACS Award for Distinguished
Service in Inorganic Chemistry Sponsored by Mallinckrodt Company; John
C. Bailar, Jr. Medal, University of Illinois; Elected to National
Institute of Medicine; Elected to National Academy of Sciences;
Alexander von Humboldt Senior U.S. Scientist Award; ACS Award in
Inorganic Chemistry Sponsored by Monsanto Company; Remson Award,
Maryland Section of the American Chemical Society; Elected Fellow,
American Academy of Arts and Sciences; Henry J. Albert Award,
International Precious Metals Institute; Chairman, Gordon Research
Conference on Inorganic Chemistry; Elected Fellow, American Association
for the Advancement of Science; Fellow of John E. Fogarty International
Center; Fellow of John Simon Guggenheim Foundation; Camille and Henry
Dreyfus Teacher-Scholar Award; Fellow of Alfred P. Sloan Foundation; NSF
Postdoctoral Fellow; NSF Predoctoral Fellow; Woodrow Wilson Honorary
Fellow; Scholastic Achievement Award, Philadelphia Section of ACS; Phi
Beta Kappa

PUBLICATIONS (498 total):

1.  Bio-inorganic chemistry Newly charted waters. Stephen J. Lippard and
    Jeremy M. Berg, Curr. Opin. Chem. Biol., 4, 137-139 (2000).

2.  DNA Sequence Context Modulates the Impact of a Cisplatin 1,2-d(GpG)
    Intrastrand Cross-link on the Conformational and Thermodynamic
    Properties of Duplex DNA. Daniel S. Pilch, Shari U. Dunham,
    Elizabeth R. Jamieson, Stephen J. Lippard, and Kenneth J.
    Breslauer, J. Mol. Biol., 296, 803-812 (2000).

3.  Modeling Carboxylate-Bridged Dinuclear Active Sites in
    Metalloenzymes Using a Novel Naphthyridine-Based Dinucleating
    Ligand. Chuan He and Stephen J. Lippard, J. Am. Chem. Soc., 122,
    184-185 (2000).

4.  Cationic Species Can Be Produced in Soluble Methane
    Monooxygenase-Catalyzed Hydroxylation Reactions; Radical
    Intermediates Are Not Formed. Seung-Yong Choi, Philip E. Eaton,
    Daniel A. Kopp, Stephen J. Lippard, Martin Newcomb, and Runnan
    Shen, J. Am. Chem. Soc., 121, 12198-12199 (1999).

5.  Synthesis of Unsymmetrical Diolate, Oxametallacyclopentene,
    Amido-Alkoxide and Thiolato-Alkoxide Complexes Using Dialkyl and
    Diaryl Titanium Aminotroponiminate Complexes: A Route to
    Unsymmetrical Vicinal Diols. Dietrich P. Steinhuebel and Stephen J.
    Lippard, J. Am. Chem. Soc., 121, 11762-11772 (1999).

6.  Amide Hydrolysis Effected by a Hydroxo-Bridged Dinickel(II) Complex:
    Insights into the Mechanism of Urease. Amy M. Barrios and Stephen J.
    Lippard, J. Am. Chem. Soc., 121, 11751-11757 (1999).

7.  Synthetic and Structural Studies of Titanium Aminotroponiminate
    Complexes. Dietrich P. Steinhuebel and Stephen J. Lippard, Inorg.
    Chem., 38, 6225-6233 (1999).

8.  NO Disproportionation Reactivity of Fe Tropocoronand Complexes.
    Katherine J. Franz and Stephen J. Lippard, J. Am. Chem. Soc., 121,
    10504-10512 (1999).

9.  Identification by NMR Spectroscopy of Residues at Contact Surfaces
    in Large, Slowly Exchanging Macromolecular Complexes. Hiroshi
    Matsuo, Kylie J. Walters, Kenta Teruya, Takeyuki Tanaka, George T.
    Gassner, Stephen J. Lippard, Yoshimasa Kyogoku, and Gerhard
    Wagner, J. Am. Chem. Soc., 121, 9903-9904 (1999).

10. Formation of Fe(III)Fe(IV) Species from the Reaction between a
    Diiron(II) Complex and Dioxygen: Relevance to Ribonucleotide
    Reductase Intermediate X. Dongwhan Lee, J. Du Bois, Doros Petasis,
    Michael P. Hendrich, Carsten Krebs, Boi Hanh Huynh, and Stephen J.
    Lippard, J. Am. Chem. Soc., 121, 9893-9894 (1999).

11. Component Interactions in the Soluble Methane Monooxygenase System
    from Methylococcus capsulatus (Bath). George T. Gassner and
    Stephen J. Lippard, Biochemistry, 38, 12768-12785 (1999).

12. Synthesis and Characterization of (Aminotroponiminato)titanium(IV)
    Dialkyl Complexes: Control of Reactivity by Ligand Design.
    Dietrich P. Steinheubel and Stephen J. Lippard, Organometallics, 18,
    3959-3961 (1999).

13. Toxicity of platinum(II) amino acid (N,O) complexes parallels their
    binding to DNA as measured in a new solid phase assay involving a
    fluorescent HMG1 protein construct readout. Christopher J. Ziegler,
    Karen E. Sandman, Cynthia H. Liang, and Stephen J. Lippard, J. Biol.
    Inorg. Chem., 4, 402-411 (1999).

14. Structural and Spectroscopic Comparisons between (-Oxo)- and
    (-Hydroxo)bis(-carboxylato)diiron(III) Complexes That Contain
    All-Oxygen-Donor Ligands. Tadashi J. Mizoguchi, Roman M. Davydov,
    and Stephen J. Lippard, Inorg. Chem., 38, 4098-4103 (1999).

15. Structure, Recognition, and Processing of Cisplatin-DNA Adducts.
    Elizabeth R. Jamieson and Stephen J. Lippard, Chem. Rev., 99,
    2467-2498 (1999).

16. Rapid fluorescence-based reporter-gene assays to evaluate the
    cytotoxicity and antitumor drug potential of platinum complexes.
    Karen E. Sandman, Sudhakar S. Marla, Gregor Zlokarnik, and
    Stephen J. Lippard, Chemistry & Biology, 6, 541-551 (1999).

17. Methylation of Iron-Sulfur Complexes by Trimethyl Phosphate.
    Jonathan J. Wilker and Stephen J. Lippard, Inorg. Chem., 38,
    3569-3574 (1999).

18. Structure of the Soluble Methane Monooxygenase Regulatory Protein B.
    Kylie J. Walters, George T. Gassner, Stephen J. Lippard, and Gerhard
    Wagner, Proc. Natl. Acad. Sci. USA, 96, 7877-7882 (1999).

19. Anticancer Activity of Cisplatin and Related Complexes. Andrew
    Gelasco and Stephen J. Lippard, Metallopharmaceuticals I: DNA
    Interactions, Topics in Biological Inorganic Chemistry, Michael J.
    Clarke and Peter J. Sadler (Eds.), Springer-Verlag: Heidelberg,
    Germany, Vol. 1, pp. 1-43 (1999).

20. Mutational and structural analyses of the regulatory protein B of
    soluble methane monooxygenase from Methylococcus capsulatus (Bath).
    Hans Brandstetter, Douglas A. Whittington, Stephen J. Lippard, and
    Christin A. Frederick, Chemistry & Biology, 6, 441-449 (1999).

**Cynthia J. Burrows, Ph.D., Professor of Chemistry, Department of
Chemistry, University of Utah**

B. A. Chemistry, 1975, University of Colorado; Ph. D. Chemistry, 1982,
Cornell University; NSF-CNRS Postdoctoral Fellow, 1981-83, Universite
Louis Pasteur, Strasbourg; Asst.Prof., Assoc. Prof., Full Prof.
1983-1994, SUNY at Stony Brook, Dept. of Chemistry; Professor of
Chemistry, 1995-present, Univeristy of Utah, Department of Chemistry.

Research Interests: Metal-mediated oxidation of DNA, particularly with
Ni, Co, Cu and Mn catalysts; metal complexes as probes of DNA and RNA
structure; metallopeptides targeted to DNA; sulfite autoxidation by
metals and resulting DNA damage; engineering metal catalytic sites into
ribozymes.

Key publications:

1.  C. J. Burrows and J. G. Muller, \"Oxidative Nucleobase Modifications
    Leading to Strand Scission,\" Chem. Rev. 1998, 98, 1109-1152.

2.  R. P. Hickerson, C. D. Watkins-Sims, C. J. Burrows, J. F.
    Atkins, R. F. Gesteland, and B. Felden, \"A Nickel Complex Cleaves
    Uridines in Folded RNA Structures: Application to E. coli tmRNA and
    Related Engineered Molecules,\" J. Mol. Biol. 1998, 279, 577-587.

3.  J. G. Muller, R. P. Hickerson, R. J. Perez, and C. J. Burrows, \"DNA
    Damage from Sulfite Autoxidation Catalyzed by a Nickel(II)
    Peptide,\" J. Am. Chem. Soc. 1997, 119, 1501-1506.

4.  K. Wietzerbin, J. G. Muller, R. A. Jameton, G. Pratviel, J.
    Bernadou, B. Meunier, and C. J. Burrows, \"Hydroxylation,
    Epoxidation and DNA Cleavage Reactions Mediated by the Biomimetic
    MnTMPyP/O2/Sulfite Oxidation System,\" Inorg. Chem. 1999,

5.  38, 4123-4127.

6.  J. G. Muller, L. A. Kayser, S. J. Paikoff, V. Duarte, N. Tang, S. E.
    Rokita, and C. J. Burrows, \"Formation of DNA adducts using
    nickel(II) complexes of redox-active ligands: A comparison of salen
    and peptide complexes,\" Coord. Chem. Rev. 1999,

7.  185-186, 761-774.

8.  A. J. Stemmler and C. J. Burrows, \"The Sal-XH Motif for
    Metal-mediated Oxidative DNA-Peptide Cross-linking,\" J. Am. Chem.
    Soc. 1999, 121, 6956-6957.

**Thomas J. Meade, Ph.D., Bechman Institute, California Institute of
Technology**

Thomas J. Meade joined the faculty of the Division of Biology and the
Beckman Institute in 1991. He received his BS and MS degrees in
chemistry and biochemistry, and a Ph.D. in inorganic chemistry in 1985
from the Ohio State University. He was awarded a NIH post-doctoral
fellowship in the department of radiology at Harvard Medical School
where he synthesized magnetic resonance imaging agents for
organ-specific tumor identification. In 1987 he assumed a postdoctoral
appointment in the division of chemistry at the California Institute of
Technology where he studied long-range electron transfer reactions in
biomolecules.

Dr. Meade\'s research interests are focused in the areas of inorganic
coordination chemistry, bioinorganic chemistry and biological imaging.
His work in electron transfer reactions through DNA led to the discovery
of a new generation of electronic biosensors of DNA. In 1995 he
cofounded Clinical Microsensors that has developed a rapid, chip-based
assay for DNA detection.

His work in magnetic resonance imaging has produced a new way to acquire
biochemical information in the form of a 3D-MR image. These contrast
agents have been shown to monitor in-vivo gene expression and detect
intracellular messengers in a noninvasive modality. In 1998 he founded
Metaprobe LLC to commercialize these agents for clinical diagnostic
radiology.

**David Piwnica-Worms, M.D., Ph.D., Professor, Program in Bioorganic
Chemistry, Washington University School of Medicine**

David Piwnica-Worms received his B.Sc. in Mechanical Engineering from
Stanford University and pursued combined M.D.-Ph.D. degrees with
dissertation studies under Prof. Melvyn Lieberman in membrane biophysics
and physiology at Duke University Medical School. After a residency in
diagnostic radiology at the Brigham and Women's Hospital and a
post-doctoral fellowship in magnetic resonance, he joined the faculty of
Harvard Medical School. He was promoted to Associate Professor before
moving to Washington University Medical School in 1994 were he is now
Professor of Radiology and Professor of Molecular Biology &
Pharmacology. His research interests include the biochemistry and
molecular pharmacology of multidrug resistance mediated by
P-glycoprotein and homologous transporters, the utility of novel
coordination complexes as radiopharmaceuticals and medicinals, as well
as translational research using radiopharmaceuticals for molecular
imaging in vivo. As Director of the Molecular Imaging Center and
Laboratory of Molecular Radiopharmacology, he leads a multidisciplinary
group of scientists focused on research investigations arising at the
interface of cancer cell biology, inorganic chemistry and the
radiopharmaceutical sciences.

Representative Publications:

1.  Sharma, V., Beatty, A., Wey, S.-P., Dahlheimer, J., Pica, C.A.,
    Crankshaw, C.L., Bass, L., Green, M.A., Welch, M.J.,
    Piwnica-Worms, D. Novel gallium(III) complexes transported by MDR1
    P-glycoprotein: potential PET imaging agents for probing
    P-glycoprotein-mediated transport activity in vivo. Chem Biol 2000;
    7:335-343.

2.  Sharma, V., Piwnica-Worms, D. Metal complexes for therapy and
    diagnosis of drug resistance. Chemical Rev 1999; 99:2545-2560.

3.  Rao, V.V., Dahlheimer, J.L., Bardgett, M.E., Snyder, A.Z., Finch,
    R.A., Sartorelli, A.C., Piwnica-Worms, D. Choroid plexus epithelial
    expression of MDR1 P-glycoprotein and multidrug
    resistance-associated protein contribute to the
    blood-cerebrospinal-fluid drug-permeability barrier. Proc Natl Acad
    Sci USA 1999; 96:3900-3905.

4.  Luker, G.D., Rao, V.V., Crankshaw, C.L., Dahlheimer, J.,
    Piwnica-Worms, D. Characterization of phosphine complexes of
    technetium(III) as transport substrates of the multidrug resistance
    MDR1 P-glycoprotein and functional markers of P-glycoprotein at the
    blood-brain barrier. Biochemistry 1997; 36:14218-14227.

5.  Goldberg, D.E., Sharma, V., Oksman, A., Gluzman, I.Y., Wellems,
    T.E., Piwnica-Worms, D. Probing the chloroquine resistance locus of
    Plasmodium falciparum with a novel class of multidentate metal(III)
    coordination complexes. J Biol Chem 1997; 272:6567-6572.

**Shubh Sharma, Ph.D., Palatin Technologies, Inc.**

Dr. Shubh Sharma is Director of Peptide Research at Palatin
Technologies, Inc. (1994-present) He is a peptide chemist with over 18
years of experience in the area of peptide research, drug design and
discovery. His recent research interest focuses on development of a
novel metallopeptide based drug development platform called "MIDAS," in
which conformationally constrained peptides and combinatorial libraries
are developed utilizing a metal ion complexed core structure. His
previous research experience include: Research Scientist (1988-1994) in
the research group of Prof. Victor J. Hruby of the University of
Arizona, Tucson, and Scientific co-worker (1984-1988), in the research
group of Prof. Robert Schwyzer, Swiss Federal Institute of Technology,
Zurich (ETH-Zurich), Switzerland. He is an inventor on 7 patents and 5
pending patent applications, and is an author on 54 publications.

**Thomas L. Poulos, Ph.D. , Professor, Department of Molecular Biology
and Biochemistry, University of California-Irvine**

B.A. in Zoology, Univ. Calif., Santa Barbara,1968; Ph.D. in Biology,
Univ. Calif., San Diego, 1973. Research Chemist, UCSD, 1973-1983;
Principal Research Scientist & Director Protein Engineering Dept, Genex
Corp, 1983 - 1987; Professor of Biochemistry, Univ. of Maryland and
Director of Center for Advanced Research in Biotechnology, 1987-1991;.
Professor of Molec. Biol. and Biochem.,Univ. Calif., Irvine,
1992-present; Director of Structural Molecular Biology Program in the
UCI Cancer Institute; Director UCI Program in Macromolecular Structure;
NIH Metallobiochemistry Study Section, 1998-present.

Research interests: Structure and function of hemeproteins; mechanisms
of heme enzyme catalyzed oxygen activation reactions and interprotein
electron transfer reactions; protein crystallography; mutagenic methods
as a probe of protein structure and function.

Selected Recent Publications:

1.  Poulos TL, Raman CS, Li H (1998). NO news is good news. Structure 6,
    255-258.

2.  Sundaramoorthy M, Terner J, Poulos TL (1998). Stereochemistry of
    chloroperoxidase active site: crystallographic and
    molecular-modeling studieses. Chemistry&Biology 5, 461-473.

3.  Mandelman D, Jamal J, Poulos TL. (1998). Identification of Two
    Electron Transfer Sites in Ascorbate Peroxidase Using Chemical
    Modification, Enzyme Kinetics, and Crystallography. Biochemistry 37,
    17610-17617.

4.  Raman CS, Li H, Martasek P, Kral V, Masters BSS, Poulos TL. (1998).
    Crystal structure of constitutive endotelial nitric oxide synthase:
    a paradigm for pterin function involving a novel metal center. Cell
    95, 939-950.

5.  Sevrioukova, IF, Li, H. Zhang, H, Peterson, JA, Poulos, TL (1999)
    Structure of a cytochrome P450-redox partner electron-transfer
    complex. Proc. Natl. Acad. Sci. USA 96, 1863-1868.

6.  Poulos TL, Li H, Raman CS (1999) Heme mediated oxygen activation in
    biology: cytochrome c oxidase and nitric oxide synthase. Current
    Opin. Chem. Biol. 3, 131-137.

7.  Schuller DJ, Wilks A, Ortiz de Montellano PR, Poulos TL (1999).
    Crystal structure of heme oxygenase. Nature. Struc. Biol. 6,
    860-867.

8.  Bonagura CA, Bhaskar B, Poulos TL Conversion of an engineered
    potassium binding site into a calcium-selective site in cytochrome c
    peroxidase J. Biol. Chem. 274, 37827-37833.

**Kenneth M. Merz, Jr., Ph.D., Professor, Department of Chemistry,
Pennsylvania State University**

B.S. in Chemistry, Washington College, 1981; Ph.D. in Organic Chemistry,
The University of Texas at Austin, 1985. Postdoctoral Scholar, Cornell
University, 1986-1987; The University of California, San Francisco,
1987-1989. Assistant (1989-1995), Associate (1995-1997), and Professor
of Chemistry (1997-present), The Pennsylvania State University. Senior
Director, The Center for Informatics and Drug Discovery, Pharmacopeia,
Inc. 1998-present.

Fellow, American Association for the Advancement of Science, 1999;
Visiting Professor, University of Strasbourg, France, 1998; John Simon
Guggenheim Fellowship, 1996-1997; Visiting Professor, University of
Strasbourg, France, 1997; Visiting Professor, University of Florence,
Italy, 1993; Office of Naval Research-Young Investigator, 1990-1993;
National Institutes of Health FIRST Award, 1991-1996; Robert A. Welch
Predoctoral Fellow, The University of Texas at Austin, 1982 to 1985;
Departmental Competitive Fellowships, The University of Texas at Austin,
1981; Robert A. Welch Summer Research Fellow, The University of Texas at
Austin, 1981.

Phi Kappa Phi; American Chemical Society; American Association for the
Advancement of Science; New York Academy of Sciences; Biophysical
Society; American Physical Society; Protein Society.

Current Research Interests:

The focus of my group is to use computational techniques to further our
understanding of biomolecular structure, function and dynamics.
Summarized below are the principal research areas that are currently
under way in the my research group.

A. Theoretical studies of the structure and function of zinc
metalloenzymes. The β-lactamases family of enzymes is of greatest
current interest. Other zinc metalloenzymes of current and past interest
include carboxypeptidase, carbonic anhydrase, liver alcohol
dehydrogenase and the zinc finger class of proteins.

B. Exploration of the utility of coupled potential calculations
(so-called QM/MM calculations). We are developing and applying new
theoretical techniques to use combined quantum and classical mechanical
techniques to study reactions in enzymes and in solution.

C. We are developing fully quantum mechanical models that can be applied
to the study of the structure and function of biomolecular systems.

Selected Publications 1998-2000 (120 total):

1.  \"Charge-Transfer Interactions in Macromolecular Systems: A New View
    of the Protein/Water Interface\" G. Nadig, L. C. Van Zant; S. L.
    Dixon; K. M. Merz, Jr *J. Am Chem. Soc* 1998, *120*, 5593-5594.

2.  \"Towards All-Electron Modeling of Biomolecular Systems\" G.
    Monard; K. M. Merz, Jr. *Acc. Chem. Res.* 1999, *32*, 904-911.

3.  \"Implementation and Testing of a Frozen Density Matrix-Divide and
    Conquer Algorithm\" M. Ermolaeva; A. van der Vaart; K. M. Merz, Jr.
    *J. Phys. Chem.* 1999, *103*, 1868-1875.

4.  \"Solvent Dynamics and Mechanism of Proton Transfer in Human
    Carbonic Anhydrase II\" S. Toba; G. Colombo; K. M. Merz, Jr. *J. Am.
    Chem. Soc* 1999, *121*, 2290-2302.

5.  \"Divide and Conquer Interaction Energy \" A. van der Vaart; K. M.
    Merz, Jr. *J. Phys. Chem.A* 1999, *103*, 3321-3329.

6.  \"Fully Quantum Mechanical Description of Proteins in Solution.
    Combining Linear Scaling Quantum Mechanical Methodologies with the
    Poisson-Boltzmann Equation\" V. Gogonea; K. M. Merz, Jr. *J. Phys.
    Chem. A.* 1999, *103*, 5171-5188.

7.  "The Role of Polarization and Charge Transfer in the Solvation of
    Biomolecules" A. van der Vaart; K. M. Merz, Jr. *J. Am. Chem. Soc.*
    1999, *121*, 9182-9190.

8.  "Charge Transfer in Biologically Important Biomolecules: A
    Comparison of High Level *ab initio* and Semiempirical Models" A.
    van der Vaart; K. M. Merz, Jr. *Int. J. Quantum Chem.* 2000,*77*,
    27-43.

9.  "A Quantum Mechanical-Poisson-Boltzmann Equation Approach for
    Studying Charge Flow Between Ions and a Continuum Dielectric" V.
    Gogonea; K. M. Merz, Jr. *J. Chem. Phys.* 2000, *104*, 2117-2122.

10. "Charge Flow Between Ions and a Dielectric Continuum: 2. Variational
    Method for Distributing Charge into the Dielectric" V.
    Gogonea; K. M. Merz, Jr. *J. Phys. Chem* 2000, *112*, 3227-3235.

11. "Analysis of Protein Folding at the Electronic Level: The Influence
    of the Local Environment on the Energetics and Charge Distribution
    of the Folding of Betanova" A. van der Vaart; K. M. Merz, Jr. *J.
    Phys. Chem.* 2000 submitted.

12. " Zinc Metallo-β-Lactamase from *Bacteroides fragilis*: A Quantum
    Chemical Study on Model Systems of the Active Site" N. Diaz; D.
    Suarez; K. M. Merz, Jr. *J. Am. Chem. Soc.* 2000 in press.

**Benjamin J. Burke, Ph.D., Senior Scientist I, Computational Chemistry,
Agouron Pharmaceuticals**

B.S. Chemistry, 1981, University of Puget Sound, Tacoma, WA.; Ph.D.
Medicinal Chemistry, University of Illinois at Chicago, March 1993.
Postdoctoral Fellow, Agouron Pharmaceuticals, November 1992-November
1993. Pennwalt Corporation, Inorganic Division, 1981-1986; Agouron
Pharmaceuticals, Inc., Research Scientist, 1993-1997;

Agouron Pharmaceuticals, Inc., Senior Scientist I, 1997-present.

Research Projects: HIV-1 Protease, Matrix Metalloprotease, Herpes, HIV-1
Integrase, MetAP2.

Research Interests:

Protein-ligand molecular recognition and binding energetics; Development
of methods for use in rational design of therapeutic agents; Application
of methods to estimate solvent effects; Statistical techniques for
solving multivariate problems; Molecular modeling; Molecular similarity;
Library design and diversity; ADMET prediction

Representative Publications (from two worlds\--QSAR and SBDD):

1.  Hopfinger, A. J., Burke, B. J., and William J. Dunn, III, A
    Generalized Formalism of Three Dimensional Quantitative
    Structure-Property Relationship Analysis for Flexible Molecules
    Using Tensor Representation, J. Med. Chem., 1994, 37, 3775-3788.

2.  P. S. Dragovich, T. J. Prins, R. Zhou, S. E. Webber, J. T.
    Marakovits, S. A. Fuhrman, A. K. Patick, D. A. Matthews, C. A.
    Lee, C. E. Ford, B. J. Burke, P. A. Rejto, T. F. Hendrickson, T.
    Tuntland, E. L. Brown, J. W. Meador, III, R. A. Ferre, J. E. V.
    Harr, M. Kosa, and S. T. Worland, Structure-based design, synthesis,
    and biological evaluation of irreversible human rhinovirus 3C
    protease inhibitors. 4. Incorporation of P1 lactam moieties as
    L-glutamine replacements J. Med Chem, 42, 7, 1213-1224.

**Shuang Liu, Ph.D., Principal Research Chemist, Medical Imaging
Division, Dupont Pharmaceuticals Company**

Shuang Liu was born in China. He received his B.S. degree in chemistry
at Shandong Normal University in 1982, and then completed his Master\'s
degree in pharmaceutical sciences at Shandong Medical University in
1985. He came to North America in 1987 to pursue his Ph.D. with
Professor Robert C. Lucas at Memorial University of Newfoundland, St.
John\'s, Canada, studying the coordination chemistry of macrocyclic
thioether ligands with various transition metals. After completion of
his Ph.D. in 1990, he spent the next two and half years as a NSERC
(Natural Sciences and Enginerring Research Council of Canada)
postdoctoral fellow with Professor Chris Orvig at the University of
British Columbia, Vancouver, Canada, investigating the coordination
chemistry of technetium, aluminum, gallium, indium, and lanthanide metal
complexes with various ligand systems. In 1993, he joined DuPont
Pharmaceuticals Company as a Senior Research Scientist. He is currently
a Principal Research Scientist

in the Medical Imaging Division (North Billerica, MA, U.S.A.). His
research

interests include receptor-based target specific radiopharmaceuticals,
new

bifunctional chelators, development of new techniques for the
radiolabeling of small

biomolecules, and coordination chemistry of metallopharmaceuticals. He
is a member of Advisory Board of Bioconjugate Chemistry,
author/co-author of 15 US patents or foreign patent applications, and
author/co-author of over 60 scientific papers.

**Carolyn J. Anderson, Ph.D., Associate Professor, Department of
Radiology, Washington University School of Medicine**

B.S. Chemistry, 1985, University of Wisconsin-Superior; Ph.D. Inorganic
Chemistry, 1990, Florida State University; Research Associate,
Washington University School of Medicine (WUSM), 1990-1992; Assistant
Professor, WUSM, 1993-2000; Associate Professor, WUSM, 2000-present.

Research Interests: Development of radiometal-labeled
radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of
cancer; development of bifunctional chelators for labeling radiometals
to biological molecules; metabolism of radiometal-labeled
bifunctional-chelate-biological molecule conjugates; mechanisms of cell
killing;

Key publications:

1.  Anderson CJ, Pajeau TS, EdwardsWB, et al. J.Nucl. Med. 1995;
    36:2315-2325.

2.  Connett JM, Anderson CJ, Guo LW, et al. Proc. Nat. Acad. Sci.,
    U.S.A., 1996; 93:6814-6818.

3.  Duncan JR, Stephenson MT, Wu HR, Anderson CJ. Cancer Res. 1997;
    57:659-671. Anderson CJ, Jones LA, Bass LA, et al. J. Nucl. Med.,
    1998; 39:1944-1951.

4.  Lewis JS, Lewis MR, Srinivasan A, Schmidt MA, Wang J, Anderson
    CJ. J. Med.Chem. 1999; 42:1341-1347.

5.  Connett JM, Buettner TL, Anderson CJ. Clin.Cancer Res. 1999;
    5:3207s-3212s. Anderson CJ, Welch, MJ. Chemical Reviews, 1999;
    99:2219-2234.

6.  Lewis JS, Lewis MR, Cutler PD, et al. Clin. Cancer Res., 1999;
    5:3608-3616

**Randall B. Lauffer, Ph.D., Chief Scientific Officer, EPIX Medical,
Inc.**

Dr. Lauffer received his Ph.D. in Chemistry from Cornell University in
1983. At the Massachusetts General Hospital, Boston, MA, he served as a
National Institutes of Health Postdoctoral Fellow and as director of the
NMR Contrast Media Laboratory. He also held positions of Assistant
Professor in Radiology at Harvard Medical School and NIH New
Investigator. In 1992, Dr. Lauffer founded EPIX Medical, Inc., a
developer of MRI contrast agents, and currently serves as Chief
Scientific Officer and a member of the board of directors.

Recent papers:

1.  Lauffer RB, Parmelee DJ, Ouellet HS, et al. \"MS-325: A
    small-molecule vascular imaging agent for magnetic resonance
    imaging.\" Acad Radiol 1996; 3:S356-S358.

2.  Parmelee DJ, Walovitch RC, Ouellet HS, Lauffer RB. \"Preclinical
    evaluation of the pharmacokinetics, biodistribution, and elimination
    of MS-325, a blood pool agent for MRI.\" Invest Radiol 1997;
    32(12):741-747.

3.  Li, D, Dolan, RP, Walovitch RC, Lauffer, RB. \"Three Dimensional MRI
    of Coronary Arteries Using and Intravascular Contrast Agent.\" MRM
    1998; 1014-1018.

4.  Lauffer RB, Parmelee, DJ, Dunham, SU, et al. \"MS-325:
    Albumin-targeted Contrast Agent for MR Angiography.\" Radiology
    1998; 207(2): 529-538.

5.  Hofman MBM, Henson RE, Kovacs SJ, et al. \"Blood Pool Agent Strongly
    Improves 3D Magnetic Resonance Coronary Angiography Using and
    Inversion Pre-Pulse.\" Magnetic Resonance in Medicine 1999;
    41:360-367.

6.  Caravan P, Ellison JJ, McMurry TJ, Lauffer RB. \"Gadolinium(III)
    Chelates as MRI Contrast Agents: Structure, Dynamics, and
    Applications.\" Chemical Reviews 1999, 99: 2293-2352.

**Richard A. Miller, M.D., President and Chief Executive Officer,
Pharmacyclics**

Dr. Miller is the President, Chief Executive Officer and a Director of
Pharmacyclics, a

public biotechnology company, which he co-founded in April 1991. In
1984, Dr.

Miller co-founded IDEC Pharmaceuticals Corporation, a public
biotechnology company,

where he served as Vice President and a Director until February 1992.
Dr. Miller

also is a Clinical Professor of Medicine (Oncology) at Stanford
University Medical

Center. Dr. Miller received his M.D., summa cum laude, from the State
University of New York Medical School and is board certified in both
Internal Medicine and Medical

Oncology.

**Thomas V. O\'Halloran, Ph.D., Professor, Department of Chemistry,
Northwestern University**

Thomas V. O\'Halloran (Born May 10,1957) is a Professor in the
Department of Chemistry and the Department of Biochemistry, Molecular
Biology and Cell Biology of Northwestern University. He is also Director
of Research in the Radiation Medicine Institute of Evanston Hospital and
serves as Director of the Molecular Oncogenesis Basic Research Group at
Northwestern's Robert E. Lurie Cancer Center.

Prof. O'Halloran's research interests center on the biology and
chemistry of transition series elements. His work focuses on the
intracellular inorganic chemistry of zinc, copper, iron and mercury. The
results provide insights into human health, cancer and disorders such as
Wilson disease and Lou Gehrig's Disease. In the course of these studies,
Prof. O'Halloran and his coworkers have characterized two new classes of
soluble metal receptors: the metalloregulatory and metallochaperone
protein. This research has been funded by NIH, NSF, ONR, The ALS
Association, The Boughton Trust and the Searle Scholars Program of the
Chicago Community Trust.

Scientific recognition includes Presidential Young Investigator Award,
NSF (1987-92); National Searle Scholars Award, The Chicago Community
Trust (1987-90), Alfred P. Sloan Research Fellow (1991-93); The Camille
and Henry Dreyfus Foundation Teacher-Scholar Award (1993-95); and
American Society of Biochemistry and Molecular Biology Scientific
Achievement Award sponsored by Schering-Plough (1996). He is a Fellow of
the American Association for the Advancement of Science and a John Simon
Guggenheim Fellow.

Professor O'Halloran's service to the academic and scientific
communities currently includes Chairmanship of the Metallobiochemistry
Review Panel of the National Institutes of Health, Chairman of the
Microbial Stress Response Gordon Conference and Chairman of the General
faculty Committee of Northwestern University. Professor O'Halloran will
be the Chairman of the Metals in Biology Gordon Conference in 2002. He
is currently on the editorial board of *Inorganic Biochemistry, Current
Opinion in Chemical Biology* and the *Journal of Biological Inorganic
Chemistry*. He has served as Chair of the Bioinorganic Subdivision of
American Chemical Society and on the board of one of its journals,
*Inorganic Chemistry*.

Prof. O'Halloran's teaching has been recognized by Mortar Board (Faculty
Honor Roll of Outstanding Teachers, 1994); the Associated Student
Government (Faculty Honor Roll, 1996); the Interfraternity Council and
Panhellenic Association (Award for Excellence in Teaching, 1997); and
the Weinberg College of the Arts and Sciences (Leroy Hall Award for
Excellence in Teaching, 1998).

Dr. O'Halloran received his bachelor's and master's degrees from the
University of Missouri, his doctoral degree in Bioinorganic Chemistry
from Columbia University, New York; and was a NRSA Postdoctoral Fellow
at MIT. He joined the Northwestern faculty in 1986.

**Elizabeth C. Theil, Ph.D., Senior Research Scientist, Children\'s
Hospital of Oakland Research Institute**

Elizabeth C. Theil is currently Senior research Scientist at CHORI, a
private research institute owned by Children's Hospital Oakland and
dedicated to basic and clinical research on diseases of children. Theil
recently joined CHORI to expand her program on BioIron by creating
interfaces for translational research on iron overload in medicine and
iron deficiency in nutrition. She chose to leave her chair as University
Professor of Biochemistry and Physics at North Carolina State University
and join CHORI because the intellectual, scientific and clinical
environment. Educated at Cornell and Columbia Universities, and author
of over 150 scientific publications, Theil is a leader in the study of
BioIron with interests that span Biology and Chemistry, both
scientifically and pedagogically. Some of her activities include:

-   Editing a new textbook "Principles of Chemistry in Biology, a tool
    for teaching connections between Biology and Chemistry;

-   Serving on editorial boards for publications at the chemistry/
    biology interface.

-   Serving as President (1998-2000) 0f SBIC, the Society of Biological
    Inorganic Chemistry, which is dedicated to expanding science and
    education in Bioinorganic Chemistry.

Ferritin, which is the model of gene regulation and protein function
that Theil has selected for study, concentrates iron as a solid inside
the protein to match cellular requirements that are \~ 10^11^ times
above the solubility of free iron. Oxygen is also trapped during
ferritin mineralization, possibly providing an oxygen trap in anerobes.
Animals, plants and bacteria all use ferritin. Ferritin pathologies in
humans are associated with thalassemia, sickle cell anemia,
hemochromatosis, cataracts, infection, and inflammation; deletion of a
ferritin gene in mice is lethal early in embryonic development. Plants
use ferritin iron for chloroplast maturation and photosynthesis.The
premier source of iron in cells for iron protein synthesis and in
organisms for normal growth and health is ferritin. Recently ferritin
has been shown to correct nutritional iron deficiency and anemia in
rats. Iron deficiency affects 30% of the world population negatively
influencing productivity, cognitive development and general health.
Ferritin is also the first line of defense against excess iron
associated with genetic diseases, including hemochromatosis, one of the
most prevalent genes in humans of European descent.

Current research studies Theil is directing include molecular studies of
the structure and function the IRE family of mRNA regulatory elements
and the entry and exit of iron into out of the ferritin protein. In
addition, both ferritin mRNA and protein are being developed as targets
for chemicals to enhance ferritin biosynthesis (mRNA) or iron chelation
(protein) in the management of iron overload. Finally, she is exploring
iron homeostasis in transgenic murine models of sickle cell and
thalassemia disease and seed ferritin as a bioavailable source of iron
in human nutrition.

Selected Publications:

1.  Sierzputowska-Gracz, H., McKenzie, R.A., and Theil, E.C. (1995) The
    Importance of a Single G in the Hairpin Loop of the Iron Responsive
    Element (IRE) in Ferritin mRNA for Structure: An NMR Spectroscopy
    Study. Nucl. Acids Res. 23, 145-152.

2.  Trikha, J., Theil, E.C., and Allewell, N.M. (1995) High Resolution
    Crystal Structures of Amphibian Red Cell L Ferritin: Potential Roles
    for Structural Plasticity and Solvation in Function. J. Mol. Biol.
    248, 949-967.

3.  Beard, J.L., Burton, J.W., and Theil, E.C. (1996) Purified Ferritin
    and Soybean Meal Can be Sources of Iron for Treating Iron Deficiency
    in Rats. J. Nutr. 126, 154-160.

4.  Proudhon, D., Wei, J., Briat, J.F., and Theil, E.C. (1996) Ferritin
    Gene Organization: Differences Between Plants and Animals Suggest
    Possible Kingdom-Specific Selective Constraints. J. Mol. Evol. 42,
    325-336.

5.  Thorp, H.H., McKenzie, R.A., Lin, P.N., Walden, W.E., and Theil,
    E.C. (1996) Cleavage of functionally relevant sites in ferritin mRNA
    by oxidizing metal complexes. Inorganic Chemistry 35, 2773-2779.

6.  Waldo, G.S. and Theil, E.C. (1996) Ferritin and Iron
    Biomineralization. IN: Comprehensive Supramolecular Chemistry,
    Vol. 5. Bioinorganic Systems (K.S. Suslick, vol. ed.) Pergamon
    Press, Oxford, UK, pp. 65-89.

7.  Pereira, A.S., Tavares, P., Lloyd, S.G., Danger, D., Edmondson,
    D.E., Theil, E.C., and Huynh, B.H. (1997) Rapid and parallel
    formation of Fe^3+^ multimers, including a trimer, during H-type
    subunit ferritin mineralization. Biochemistry 36, 7917-7927.

8.  Theil, E.C., (1997) Translational regulation of iron metabolism in
    animals. IN*:* Metal Regulation of Gene Expression (S. Silver and
    W.E. Walled, eds.), Chapman Hall, New York, NY, pp. 131-156

9.  Theil, EC, Burton, J.W. and Beard, J.L. (1997) A sustainable
    solution for dietary iron deficiency through plant biotechnology and
    breeding to increase seed fourteen control. Euro. J. Clin. Nut. 51,
    S28-S31.

10. Ha, J., Theil, EC, and Allewell, N.M. (1997) The structure of red
    cell M fourteen in a novel tetragonal unit cell. ACTA Crystall.
    Section D53 (part 5), 513-523.

11. Theil, E.C. (1998) The iron responsive element (IRE) family of mRNA
    regulators in mRNA. IN: Metal Ions in Biological Systems. Vol. 35,
    (A. Sigel and H. Sigel, eds.). Marcel Dekker, Inc. New York,
    403-434.

12. Gdaniec, Z., Sierzputowska-Gracz, H. and Theil, E.C. (1998)
    Structure of the IRE (Iron responsive element) in ferritin mRNA. An
    NMR and modeling study. Biochemistry 37, 1505-1512.

13. Y. Ke, Wu, J., Leibold,E.A., Walden, W.E. and Theil, E.C. (1998)
    Loops and Bulge/Loops in Iron-responsive Element Isoforms Influence
    Iron Regulatory Protein Binding. J. Biol.Chem. 273, 23673- 23640

14. Pereira, A., Small, G.S., Krebs, C., Tavares, P., Edmondson, D.E.,
    Theil, E.C., and Huynh, B.H. (1998) Direct Spectroscopic and Kinetic
    Evidence for the Involvement of a Peroxodiferric Intermediate during
    the Ferroxidase Reaction in Fast Ferritin Mineralization.
    Biochemistry 37, 9871-9876.

15. Takagi, H., Shi, D., Hall, Y., Allewell, N.M., and Theil,
    E.C. (1998) Localized Unfolding at the Junction of Three Ferritin
    Subunits. J. Biol. Chem. 273, 18685-18688.

16. Cliftan, S.A., Theil, E.C., and Thorp, H.H. (1998) Oxidation of
    Guanines in the Iron Responsive Element RNA: Similar Structures from
    Chemical Modification and recent NMR Studies. Chemistry and Biology
    5, 679-687.

17. Theil, E.C., Ke, Y., Wei, J., and Takagi, H. (1999) Ferritin:
    constant and variable features of structure/function and gene
    regulation. IN: Iron Metabolism: Inorganic Biochemistry and
    Regulatory Mechanisms. (G.C. Ferreira, J.J.G. Moura, R. Franco,
    eds.) WILEY-VCH Verlag GmbH, Federal Republic of Germany, 187-198.

18. Moënne-Loccoz, P., Krebs, C., Herlihy, K., Edmondson, D.E., Theil,
    E.C., Huynh, B.H. and Loehr, T.M. (1999) The Ferroxidase Reaction of
    Ferritin Reveals a Diferric μ-1,2 Bridging Peroxide Intermediate in
    Common with Other 0~2~ --Activating Non-Heme Diiron Proteins.
    Biochemistry 38, 5290-5295.

19. Ha,Y., Shi, D. Small, G.W., Theil, E.C. and Allewell, N.M. (1999)
    Crystal Structure of Bullfrog M Ferritin at 2.8 A Resolution:
    Analysis of Subunit Interactions and a Binuclear Metal Center J.
    Biol. Inorg. Chem. 4, 243-256.

20. Theil, E.C., Ke, Y., Gdaniec, Z. and Sierzputowska-Gracz, H. (1999)
    The IRE model for families of RNA structures: Selective recognition
    by binding proteins (IRPs), NMR spectroscopy and probing with metal
    coordination complexes. IN: RNA Biochemistry and Biotechnology. (J.
    Barciszewski and B.F.C. Clark, eds.) Kluwer Academic Publishers,
    Netherlands, 241-247.

21. Theil, E.C. (2000) Targeting mRNA to regulate Iron and Metabolism.
    Biochemical Pharmacology 59, 87-93.

22. Theil, E.C., Small, G.W., He, L., Tipton, A.R. and Danger, D. (2000)
    The ferritin iron entry and exit problem. Inorganica Chimica Acta
    297, 242-251.

23. Hwang, J., Krebs, C., Huynh, B.H., Edmondson, D.E., Theil, E.C. and
    Penner-Hahn, J.E. (2000) A Short Fe-Fe Distance in Peroxodiferric
    Ferritin: Control of Fe Substrate Versus Cofactor Decay? Science
    287, 122-125.

**Kenneth N. Raymond, Ph.D., Professor of Chemistry, Department of
Chemistry, University of California**

Professor Kenneth N. Raymond was born on January 7, 1942 in Astoria,
Oregon. Following his early education in the public schools of Oregon,
he attended Reed College where he received a B.A. in 1964. His education
was interrupted by a one-year stay in Europe, where he was a test driver
and mechanic in Munich. Upon completing his Ph.D. he began his faculty
appointment at the University of California at Berkeley on July 1, 1967.
There he has remained, becoming Associate Professor in 1974 and
Professor in 1978. He has served as Vice Chair of the Berkeley Chemistry
Department (1982-1984 and 1999-2000) and Chair (1993-1996). He has been
a Visiting Professor or Lecturer at several universities. These include:
Stanford University (1973), The Australian National University (1974),
Université Louis Pasteur, Strasbourg (1980), University of Rennes
(1988), University of Queensland (1989), William Pyle Phillips
Distinguished Visitor, Haverford College (1993), 3\`eme Cycle Lecturer
in Switzerland (1990,1995), Patrick Lecturer, Kansas State University
(1996), Endowed Lecturer, University of Oklahoma (1987, 1996), Ernest H.
Swift Lecturer, California Institute of Technology (1996) and Sacconi
Lecturer, University Florence. He was Chair of the American Chemical
Society, Division of Inorganic Chemistry in 1996. He has been an Alfred
P. Sloan research fellow (1971-1973), a Miller research professor at the
University of California (1977-1978, 1996) and a Guggenheim fellow
(1980-1981). He received the Ernest O. Lawrence Award of the Department
of Energy in 1984, a Humboldt Research Award for Senior U.S. Scientists
in 1991, the American Chemical Society Alfred Bader Award in
Bioinorganic or Bioorganic Chemistry in 1994. He was elected to the
National Academy of Sciences in 1997. He was also selected Basolo
Medalist at Northwestern University in 1997 and received the
Max-Planck-Institut für Strahlenchemie "Frontiers in Biological
Chemistry" award.

Professor Raymond is a member of the editorial board of several journals
in the fields of inorganic and bioinorganic chemistry. In addition to
his academic appointment on the University of California campus, he is a
Faculty Senior Scientist of the Chemical Sciences Division, Lawrence
Berkeley National Laboratory. He is the author of ten patents and over
310 research publications.

Early in his career at Berkeley, Professor Raymond determined the
structure of uranocene (then newly prepared by Streitwieser and
coworkers) and went on to characterize structurally a large number of
other organo-actinide and organo-lanthanide compounds. He completed his
contribution to this field with the development of an ionic radii model
that successfully predicted these molecular structures and which
continues to be used in this growing area of organometallic chemistry.
Professor Raymond is a pioneer of the field of bioinorganic chemistry
with his research in biological iron transport, particularly siderophore
mediated iron transport in microorganisms. The characteristics of
coordination chemistry of the siderophores, and the role that molecular
recognition plays in microbial iron transport, have been major
contributions of Raymond\'s research. He and his research group were the
first to use kinetically inert metal-substituted complexes of
siderophores to elucidate the cellular transport mechanisms of iron in
microorganisms. Using such complexing agents as prototypes, Professor
Raymond and coworkers have designed and synthesized sequestering agents
specific for individual metal ions. In the case of plutonium the similar
chemical and biochemical properties of Pu(IV) and Fe(III) (which is a
basis for the biohazard of plutonium) has been exploited by Raymond and
coworkers to prepare ligands that are highly specific for Pu(IV).
Several of these compounds have been shown to be highly effective Pu
decontamination agents. A focus of Raymond\'s current research is using
coordination chemistry as the driving force in the rational design and
preparation of symmetry-driven supramolecular assemblies. The host-guest
chemistry of these supermolecules presents new opportunities for
chemical reactions.

Relevant Publications (1996-present):

1.  P. W. Durbin, B. Kullgren, N. Jeung, J. Xu, S. J. Rodgers and K. N.
    Raymond. \"Octadentate Catecholamide Ligands for Pu(IV) based on
    Linear or Preorganized Molecular Backbones." *Human & Experimental
    Toxicology* 1996, 15, 352-360.

2.  Zhiguo Hou, Christopher J. Sunderland, Takayuki Nishio and
    Kenneth N. Raymond, \"Preorganization of Ferric Alcaligin, Fe2L3,
    the First Structure of a Ferric Dihydroxamate Siderophore." *J. Am.
    Chem. Soc.* 1996, *118,* 5148-5149.

3.  Thomas Beissel, Ryan E. Powers and Kenneth N. Raymond
    \"Symmetry-Based Metal Complex Cluster Formation.\" *Angew. Chem.,*
    1996, *108,* 1166-1170. *Angew. Chem. Int. Ed. Engl.* 1996 *35,*
    1084-1086.

4.  Stefan Rupprecht, Klaus Langemann, Thomas Lügger, James M. Mccormick
    and Kenneth N. Raymond. \"Coordination Chemistry of
    Bis-thiohydroxamic Acids: Synthesis and Characterization of Their
    Lead(II) Complexes and Stability Constant Determination.\" *Inorg.
    Chim. Acta.* 1996, *243,* 79-90

5.  Berthold Kersting, Jason R. Telford, Michel Meyer and Kenneth N.
    Raymond. \"Gallium(III) Catecholate Complexes as Probes for the
    Kinetics and Mechanism of Inversion and Isomerization of Siderophore
    Complexes." *J. Am. Chem. Soc.* 1996, 118, 5712-5721.

6.  Berthold Kersting, Michel Meyer, Ryan E. Powers and Kenneth N.
    Raymond, \"Dinuclear Catecholate Helicates: Their Inversion
    Mechanism\". *J. Am. Chem. Soc.* 1996, *118*, 7221-7222

7.  Jason R. Telford and Kenneth N. Raymond. \"Siderophores." In:
    *Comprehensive Supramolecular Chemistry;* Atwood, J. L.,
    Davies, J. E. D., MacNicol, D. D. and Vogtle, F. Eds.; Elsevier
    Science Ltd.: Oxford*,* 1996, Vol. 1, pp 245-266.

8.  Ryan E. Powers, William L. Fuller III and Kenneth N. Raymond
    \"Stereognostic Coordination Chemistry." In *Comprehensive
    Supramolecular Chemistry*. Atwood, J. L., Davies, J. E. D.,
    MacNicol, D. D. and Vogtle, F. Eds.; Elsevier Science Ltd.:
    Oxford*,* 1996, Vol. 10, pp. 537-555.

9.  Klaus Langemann, Daniel Heineke, Stefan Rupprecht and Kenneth N.
    Raymond \"Nordesferriferrithiocin. Comparative Coordination
    Chemistry of a Prospective Therapeutic Iron Chelating Agent."
    *Inorg. Chem.,* 1996, *35*, 5663-5673.

10. Kenneth N. Raymond, Dana L. Caulder, Ryan E. Powers, Thomas Beissel,
    Michel Meyer and Berthold Kersting. "Coordination Number
    Incommensurate Cluster Formation." Proc. Robert A. Welch Found.
    Conf. on Chem. Res. 1996, *40,* 115-129.

11. Patricia W. Durbin, Birgitta Kullgren, Jide Xu and Kenneth N.
    Raymond. "New Agents for *In Vivo* Chelation of Uranium(VI):
    Efficacy and Toxicity in Mice of Multidentate Catecholate and
    Hydroxypyridinonate Ligands." *Health Phys.,* 1997, *72,* 865-879.
    LBL-39154

12. Dana L. Caulder and Kenneth N. Raymond. "Supramolecular
    Self-Recognition and Self-Assembly in Gallium(III) Catecholamide
    Triple Helices." *Angew. Chem. Int. Ed. Engl.,* 1997, *36,*
    1439-1442.

13. Zhiguo Hou, T.D.P. Stack, Christopher J. Sunderland, Kenneth N.
    Raymond. "Enhanced Iron(III) Chelation Through Ligand
    Predisposition: Syntheses, Structures and Stability of
    Tris-catecholate Enterobactin Analogs\". *Inorg. Chim. Acta.* 1997,
    *263,* 341-355.

14. Michel Meyer, Jason R. Telford, Seth M. Cohen, David J. White, Jide
    Xu, and Kenneth N. Raymond. \"High-Yield Synthesis of the
    Enterobactin Trilactone and Evaluation of Derivative Siderophore
    Analogs\". *J. Am. Chem. Soc.* 1997, *119,* 10093-10103.

15. Michel Meyer, Berthold Kersting, Ryan E. Powers and Kenneth N.
    Raymond. "Rearrangement Reactions in Dinuclear Triple Helicates".
    *Inorg. Chem.* 1997, *36,* 5179-5191*.*

16. Jason R. Telford and Kenneth N. Raymond. "Amonabactin: A Family of
    Novel Siderophores from a Pathogenic Bacterium". *J. Biol. Inorg.
    Chem.* 1997, *2,* 750-761.

17. Seth M. Cohen, Michel Meyer, and Kenneth N. Raymond. "Enterobactin
    Protonation and Iron Release: Hexadentate Tris-Salicylate Ligands as
    Models for Triprotonated Ferric Enterobactin". *J. Am. Chem. Soc.*
    1997, *120,* 6277-6286.

18. Christian Brückner, Ryan E. Powers, and Kenneth N.
    Raymond."Symmetry-Driven Rational Design of a Tetrahedral
    Supramolecular Ti~4~L~4~ Cluster". *Angew. Chem. Int. Ed.* 1998,
    *37,* 1837-1839.

19. Dana L. Caulder, Ryan E. Powers, Tatjana N. Parac and Kenneth N.
    Raymond. "The Self-Assembly of a Pre-designed Tetrahedral M~4~L~6~
    Supramolecular Cluster". *Angew. Chem. Int. Ed.* 1998, *37,*
    1840-1843.

20. Tatjana N. Parac, Dana L. Caulder, and Kenneth N. Raymond."Selective
    Encapsulation of Aqueous Cationic Guests into a Supramolecular
    Tetrahedral \[M~4~L~6~\]^12-^ Anionic Host". *J. Am. Chem. Soc.*
    1998, *120,* 8003-8004.

21. Jason R. Telford and Kenneth N. Raymond "Coordination Chemistry of
    the Amonabactins, Bis(catecholate) Siderophores from *Aeromonas
    hydrophila". Inorg. Chem.* 1998 *37,* 4578-4583.

22. P. W. Durbin, B. Kullgren, J. Xu and K. N. Raymond. "Development of
    Decorporation Agents for the Actinides." *Radiation Protection
    Dosimetry* 1998, *79*, 433-443.

23. Zhiguo Hou, Kenneth N. Raymond, Brendon O'Sullivan, Todd W. Esker,
    and Takayuki Nishio. "A Preorganized Siderophore: Thermodynamic and
    Structural Characterization of Alcaligin and Bisucaberin, Microbial
    Macrocyclic Dihydroxamate Chelating Agents." *Inorg. Chem.* 1998*,
    37,* 6630-6637.

24. Jide Xu and Kenneth N. Raymond. "Uranyl Sequestering Agents:
    Correlation of Properties and Efficacy with Structure for UO~2~^2+^
    Complexes of Linear Tetradentate 1-Methyl-3-Hydroxy-2(1H)-Pyridinone
    Ligands." *Inorg. Chem.* 1999, *38*, 308-315.

25. Thomas Beissel, Ryan E. Powers, Tatjana N. Parac, and Kenneth N.
    Raymond. "Dynamic Isomerization of a Supramolecular Tetrahedral
    M~4~L~6~ Cluster." *J. Am. Chem. Soc.* 1999, *121*, 4200-4206.

26. Dana L. Caulder and Kenneth N. Raymond. "The Rational Design of High
    Symmetry Coordination Clusters." *J. Chem. Soc., Dalton Trans.*
    1999, *8*, 1185-1200.

27. Markus Scherer, Dana L. Caulder, Darren W. Johnson and Kenneth N.
    Raymond. "Triple Helicate­---Tetrahedral Cluster Interconversion
    Controlled by Host-Guest Interactions." *Angew. Chem. Int. Ed.
    Engl.* 1999, *38*, 1588-1592.

28. Jide Xu, Tatjana N. Parac and Kenneth N. Raymond. "*Meso* Myths:
    What Drives Assembly of Helical versus Meso M~2~L~3~ Clusters?"
    *Angew. Chem.* *Int. Ed*. *Engl.* 1999, *38*, 2878-2882

29. Dana L. Caulder and Kenneth N. Raymond. "Supermolecules by Design."
    *Accounts of Chemical Research* 1999*,* *32*, 975-982.

**Richard A. Anderson, Ph.D., Lead Scientist, USDA, Beltsville Human
Nutrition Research, United States Department of Agriculture**

Lead Scientist at the Beltsville Human Nutrition Research Center
studying the nutritional role of chromium and other trace elements in
human health and disease. Research includes determining the effects of
various forms of stress including high sugar diets, exercise,
temperature and physical trauma on trace element metabolism. Studies are
conducted on humans, large and small animals and cell culture studies.

**Max Costa, Ph.D., Professor and Chairman, Department of Environmental
Medicine, NYU School of Medicine**

My research interests center along the molecular mechanisms of nickel
and chromium carcinogenesis. These two metals differ strikingly in their
carcinogenic action. The most carcinogenic nickel compounds are the
water-insoluble compounds that become phagocytized by cells and deliver
high concentrations of nickel inside the cell. Nickel is able to induce
chromosomal aberrations and also causes DNA hypermethylation which
inactivates the transcription of tumor suppressor genes. In yeast,
nickel is capable of silencing genes placed near the telomere binding
element. Chromium has a very different mechanism of action in that it
forms DNA adducts and crosslinks amino acids, such as cysteine,
glutathione, and protein to DNA. Chromate appears to be doing this by
binding to the phosphate backbone of DNA and preferentially binds to
guanine as well. The Cr-DNA adducts are quite stable, however, they can
be removed by EDTA and we have used UvrABC in combination with
ligation-mediated PCR to map Cr-DNA adducts in collaboration with Dr. E.
Tang in our department.

Representative Publications:

1.  Zhitkovich, A., Voitkun, V., Kluz, T., and Costa, M. Utilization of
    DNA-protein crosslinks as a biomarker of chromium exposure. Environ.
    Health Perspect. 106(4):969-974 (1998).

2.  Broday, L., Lee, Y-W., and Costa, M. 5-Azacytidine induces transgene
    silencing by DNA methylation in Chinese hamster cells. Mol. Cell
    Biol. 19(4):3198-3204 (1999).

3.  Broday, L., Cai, J., and Costa, M. Nickel enhances telomeric
    silencing in Saccharomyces cerevisiae. Mutat. Res. 440:121-130
    (1999).

4.  Salnikow, K., Blagosklonny, M., Ryan, H., Johnson, R. and Costa, M.
    Carcinogenic nickel induces genes involved with hypoxic stress.
    Cancer Res. 60:38-41 (2000).

5.  Broday, L., Peng, W., Kuo, M-H., Salnikow, K., Zoroddu, M., and
    Costa, M. Nickel compounds are novel inhibitors of histone H4
    acetylation. Cancer Res. 60:238-241 (2000).

**Chris Orvig, Ph.D., Professor of Chemistry and Pharmaceutical
Sciences, Department of Chemistry, University of British Columbia**

Chris Orvig was born and raised in Montréal. He received his B.Sc. in
chemistry from McGill University in 1976 and, after a year as an
itinerant skier, he subsequently pursued graduate studies (as a Natural
Sciences and Engineering Research Council - NSERC -- of Canada scholar)
in technetium chemistry at M.I.T. with Prof. Alan Davison, receiving the
Ph.D. in 1981.  He was then an NSERC postdoctoral fellow with Prof.
Kenneth N. Raymond at the University of California, Berkeley in 1981-83.
After one year with the late Prof. Colin J. L. Lock at McMaster
University, he joined the University of British Columbia in 1984, where
he is now Professor of Chemistry and Pharmaceutical Sciences, and
Director of the Medicinal Inorganic Chemistry Group. His scientific
interests are firmly planted in the areas of medicinal inorganic
chemistry and coordination chemistry -- he has been involved over the
years with radiopharmaceutical chemistry, metal ion decorporation, metal
ion neurotoxicology, and chemotherapeutic metal complexes.

Orvig is the inorganic chemistry editor of *Can. J. Chem.* and sits on
numerous editorial boards. He has received various research and teaching
awards, has published more than 100 research papers, is a co-inventor on
many issued patents (including eight from the USA), and is a certified
ski instructor. He is, until late summer 2000, on sabbatical leave as a
Humboldt Research Award winner in Münster, Germany with Prof. Dr. F. E.
Hahn, and travelling the world delivering lectures.

Representative Publications:

1.  D. S. Edwards, S. Liu, D. M. Lyster, M. J. Poirier, C. Vo, G. A.
    Webb, Z. Zhang, C. Orvig. Potential 99mTc Radiopharmaceuticals for
    Renal Imaging:
    Tris(*N*-substituted-3-hydroxy-2-methyl-4-pyridinonato)technetium(IV)
    Cations. *Nucl. Med. Biol.* 1993, *20*, 857.

2.  W. R. Harris, G. Berthon, J. P. Day, C. Exley, T. P. Flaten, W. F.
    Forbes, T. Kiss, C. Orvig, P. F. Zatta. Speciation of Aluminum in
    Biological Systems. *J. Toxicol. Environ. Health.* 1996, *48*, 543.

3.  K. W. Schönholzer, R. A. L. Sutton, V. R. Walker, V. Sossi, M.
    Schulzer, C. Orvig, E. Venczel, R. R. Johnson, D. Vetterli, B.
    Dittrich-Hannen, P. Kubik, M. Suter. Intestinal Absorption of Trace
    Amounts of Aluminum in Rats Studied with 26Al and Accelerator Mass
    Spectrometry. *Clin. Sci.* 1997, *92*, 379.

4.  A. Setyawati, K. H. Thompson, V. G. Yuen, Y. Sun, M. Battell, D. M.
    Lyster, C. Vo, T. J. Ruth, S. Zeisler, J. H. McNeill, C. Orvig.
    Kinetic Analysis and Comparison of Uptake, Distribution, and
    Excretion of 48V-labeled Compounds in Rats. *J. Appl. Physiol.*
    1998, *84*, 569.

5.  C. Orvig, M. J. Abrams. Eds. *Chem. Rev.*1999, *99(9)*, special
    issue on Medicinal Inorganic Chemistry.

6.  S. A. Dikanov, B. D. Liboiron, K. H. Thompson, E. Vera, V. G.
    Yuen, J. H. McNeill, C. Orvig. In Vivo Electron Spin-Echo Envelope
    Modulation (ESEEM) Spectroscopy: First Observation of Vanadyl
    Coordination to Phosphate in Bone. *J. Amer. Chem. Soc.* 1999,
    *121*, 11004.

**Dennis P. Riley, Ph.D., Vice-President for Research & Development,
Research and Development, MetaPhore Pharmaceuticals, Inc.**

Dennis P. Riley joined MetaPhore Pharmaceuticals, Inc. as Vice-President
of R&D in April, 1999. MetaPhore Pharmaceuticals is focused on the
development of both chelation therapies and the use of metal complexes
as pharmaceuticals; especially small molecule functional enzyme mimics.
He joined MetaPhore following his career at Monsanto as a Senior Science
Fellow and manager of Metal-Mediated Chemistry in Monsanto\'s Corporate
Research Division. He completed his undergraduate education with majors
in chemistry and mathematics (cum laude) at Heidelberg College and
earned his Ph.D. at Ohio State University in inorganic coordination
chemistry in 1975 with Professor Daryle Busch. Following post-doctoral
training in homogeneous catalysis at the University of Chicago in the
laboratories of Professor Jack Halpern and several years at Procter &
Gamble (becoming Section Head for process chemistry and bioinorganic
chemistry), he joined Monsanto\'s Corporate Research center in St. Louis
as Senior Research Group leader in Homogeneous Catalysis. Dr. Riley is
an Adjunct Professor of chemistry at Washington University, has been
elected a Fellow of the American Association for the Advancement of
Science, elected Chairperson and organizer of the 1998 Gordon Research
Conference on Inorganic Chemistry, and he was the recipient of the ACS
St. Louis Section\'s \'Chemist of the Year\' Award for 1999. His primary
research interests include bioinorganic chemistry (Synzymes \--small
molecule functional mimics of enzymes), activation of small molecules
(i.e., O~2~ and CO~2~), catalytic oxidations, and asymmetric catalytic
conversions. He has been granted over thirty US patents and over 200
foreign patents; as well as published over 80 papers and authored
several review articles and book chapters.

**Craig L. Hill, Ph.D., Goodrich C. White Professor, Department of
Chemistry, Emory University**

Craig L. Hill received his Ph.D. from M.I.T. in 1975 under the direction
of George M. Whitesides. After a NSF postdoctoral fellowship at Stanford
with Richard H. Holm, and an Assistant Professorship at the University
of California at Berkeley, he joined the faculty at Emory University
where he is currently Goodrich C. White Professor. His research
interests include the design of catalysts for challenging or
environmentally benign processes, and the design of catalytic systems
(both molecules and materials) that buffer themselves, repair damage and
catalyze more than one reaction (\"intelligent\" catalysts) (funded by
NSF, ARO, ONR, DOE and industry). His group also investigates the
fundamental chemical, physical and biological properties of large
multicomponent and multifunctional molecules such as polyoxometalates
(funded by NIH, ARO, and industry). One subset of this is the mechanisms
of action of polyoxometalate antiviral agents. His recent awards include
a Humboldt Senior Scientist Award (1995), the USDA National Award for
Group Excellence in Research (shared with colleagues at the Forest
Products Laboratory) (1996) for the development of a new pollution-free
catalytic aerobic technology to convert trees (wood pulp) to paper, and
the Albert E. Levy Award from Sigma Xi (1996). Currently or recently he
has served several journals (editing or editorial boards) and national
panels (NAS, NSF and NIH). He enjoys time with his domestic and research
families and yearly mountaineering and other adventures in the Americas
and Eurasia.

**Jill I. Johnson, Special Assistant to the Associate Director, DTP,
Division of Cancer Treatment and Diagnosis, National Cancer Institute**

Jill Johnson has worked for the Developmental Therapeutics Program for
more than 20 years. For the majority of this time she has assisted the
Program in the acquisition of compounds for screening as potential
anti-cancer agents, and is therefore very familiar with the history of
the screening program. She has managed the plating of the DTP repository
of \>140,000 non-proprietary compounds, and managing the distribution of
this resource to approved researchers in the extramural community. Jill
was recently promoted to the position of Special Assistant to the
Associate Director of DTP, which involves creating liaisons with the
anti-cancer research community and setting program short and long-term
goals.

## 

## 

## Nicholas P. Farrell, Ph.D., Professor, Department of Chemistry, Virginia Commonwealth University

Distinguished Scholar, Virginia Commonwealth University, 1997; Juckett
Fellowship of Vermont Cancer Center, 1992/1993; Postdoctoral
Fellowships: Simon Fraser University, Vancouver, B.C., Canada, Studies
on Aryldiazonium Metal Complexes (D. Sutton);

University of British Columbia, Vancouver, B.C., Canada, Studies on
Ruthenium Porphyrins (D. Dolphin/B.R. James).

Ph.D. Chemistry, Sussex University, Brighton, England 1973.
B.Sc. Chemistry/Mathematics (Hons.), University College, Dublin, Ireland
1969.

Selected publications (from 17 primary patents, a total of over 60
continuations-in-part, sub-divisionals and selections; 3 books and 130
refereed papers and reviews):

1.  Platinum-Based Drugs in Cancer Therapy, Kelland, L.R. and
    Farrell, N. Eds., in "Cancer Drug Discovery and Development",
    Teicher, B.A., Ed. Humana Press (2000). ISBN 0896035999

2.  Uses of Inorganic Chemistry in Medicine, Farrell, N., Ed., Royal
    Society of Chemistry (1999). ISBN 0 85404 444 2.

3.  Transition Metal Complexes as Drugs and Chemotherapeutic Agents,
    Farrell, N. in "Catalysis By Metal Complexes", James, B.R. and Ugo,
    R., Eds., Kluwer Academic Press (1989). ISBN 9027728283.

4.  Davies, M.S., Cox, J., Berners-Price, S.J., Barklage, W., Qu, Y. and
    Farrell, N.: Equilibrium and Kinetic Studies of the aquation of the
    Dinuclear Platinum Complex
    \[{trans-PtCl(NH~3~)~2~}~2~μ-NH~2~(CH~2~)~6~NH~2~\]^2+^: pK~a~
    Determinations of aqua ligands via \[^1^H,^15^N\] NMR Spectroscopy.
    Inorg. Chem. 39:1710-1715 (2000).

5.  Brabec, V., Kašpárková, J., Vrána, O., Nováková, O., Cox, J., Qu, Y.
    and Farrell, N.: DNA Modifications by a Novel Bifunctional
    Trinuclear Platinum Phase I Anticancer Agent. Biochemistry, 38,
    6781-6790 (1999).

6.  Kasparkova, J., Farrell, N. and Brabec, V.: Sequence Specificity,
    Conformation and Recognition by HMG1 Protein of Major DNA
    Interstrand Cross-Links of Antitumor Dinuclear Platinum
    Complexes. J. Biol. Chem., In Press.

7.  Farrell, N.: Current Status of Structure-Activity Relationships of
    Platinum Anticancer Drugs. Activation of the trans Geometry. Metal
    Ions in Biol. Sys., 32:603 (1996).

**David A. Place, Ph.D., Chemist, Center for Drug Evaluation Research,
Food and Drug Administration**

BS, Chemistry, UC Berkeley, 1976; PhD, Inorganic Chem, Syracuse Univ.,
1983;

NCI Fellow, Radiochem and MRI agents, Johns Hopkins Medical Inst.,
1984-89;

Guest Researcher, NCI, MRI agents, 1988-89; Research Associate, MRI
agents,

Georgetown Univ., 1990-91, Chemistry Reviewer, Div. of Medical Imaging
and

Radiopharmaceutical Drug Products, CDER, FDA, 1991-present.

**Michael J. Abrams, Ph.D., President and Chief Executive Officer,
AnorMED, Inc.**

Dr. Abrams has been active in the discovery and development of novel
metal-based drugs throughout his career. Dr. Abrams is an inventor on
the patents that led to the development of the DuPont technetium-99m
heart imaging agent, Cardiolite and is a co-inventor on JM 216, an
orally administered platinum anti-tumour agent. In 1991, Dr. Abrams was
promoted to Manager, Biomedical Research, worldwide for Johnson Matthey
PLC (together with its affiliates, "JM"). He is a named inventor on 15
patents and has authored over 50 scientific articles. He received his
Ph.D. in Chemistry from the Massachusetts Institute of Technology.

POSTER

ABSTRACTS

(By Related Meeting Session)

**Session 1. Molecular and Cellular Targets of Metal Action**

**1. Binding of HMG-domain Proteins in Purine-Rich Platinated DNA**

> Seth M. Cohen, Yuji Mikata, and Stephen J. Lippard. Department of
> Chemistry,Massachusetts Institute of Technology, Cambridge,
> Massachusetts, USA, 02139.

The HMG-domain proteins recognize and bind to cisplatin-modified DNA.
The binding affinity of these proteins for cisplatin adducts is
modulated by the specific structure of the protein and the sequence
context of the platinum adduct. The binding of several HMG-domain
proteins to platinum lesions with purine-rich flanking sequences will be
presented. These studies elucidate some of the structural features
important for high-affinity protein binding. The work further indicates
the influence and importance of sequence context on protein interactions
with cisplatin-modified DNA. These studies contribute to elucidating the
cytotoxic mechanism of the drug.

**2. Laser-Induced Photocross-linking of Cisplatin-Modified DNA to
Damage**

**Recognition Proteins**

> Yuji Mikata and Stephen J. Lippard. Massachusetts Institute of
> Technology, Cambridge, MA, USA.

We found that irradiation of mixture of the cisplatin-modified 15-mer
oligonucleotide (5\'-CCTCTCTG\*G\*TTCTTC-3\')-(5\'-GAAGAACCAGAGAGG-3\'),
where G\* denotes cisplatin-modified guanine, and HMG domain B forms
DNA-protein cross-link upon irradiation at 325 nm. There was no DNA-DNA
interstrand cross-linking, which had been found upon irradiation with a
transilluminator at 302 nm \[S. A. Kane & S. J. Lippard, Biochemistry,
35, 2180 (1996)\]. This finding allows additional structural information
to be obtained about the complexes formed between HMG-domain proteins
and cisplatin-modified DNA.

**3. Computational Analysis of All the Possible Configurational/Binding
Geometries**

> **of Co(III) Bleomycins**
>
> Marc Zimmer. Dept of Chemistry, Connecticut College, New London,
> Connecticut, USA, 06320.

No crystal structure for metallobleomycin exists, and the exact
coordination mode of the ligand is unknown. To date, spectroscopic
investigations of BLM complexes and crystal structures of BLM analogues
have been used to propose metal coordination sites. This has led to
contradictory interpretations of the metal coordination sphere in BLM.
In this paper inorganic molecular mechanics and a new inorganic
configurational/conformational/binding geometry search method was used
to analyze HOO-CoBLM A2 ; H~2~O-CoBLM A2 ; and HOO-CoPEP with all
proposed binding and configurational geometries. Nine searches were
required to analyze all 60 binding geometries/configurations.

**4. The Bioinorganic-Biomedical Interface of the Redox Active Antitumor
Agent**

> **Iron Bleomycin**
>
> D.H. Petering, P. Fulmer, W. Li, C. Xia, and C. Zhao, B. Feinberg,
> W.E. Antholine, Dept. of Chemistry, University of Wisconsin-Milwaukee,
> Milwaukee, WI 53201 and the National Biomedical ESR Center, Medical
> College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226

The clinically useful antitumor agent bleomycin (Blm) requires Fe to
carry out DNA strand scission. Its cytotoxic activity against HL-60
cells also depends on the availability of cellular Fe as shown by
experiments in Fe-deficient cells. FeBlm is the preferable form of the
drug against the Ehrlich ascites tumor in mice, possibly because it does
not need to compete for Fe from the organism. Once present in the cell
in low concentration, activation of Fe(III)Blm involves reduction of
Fe(III)Blm (E~o~\'=113 mV) and O~2~^-^Fe(II)Blm (E~o~\'=250 mV). The
kinetics of reductive activation differ at specific and non-specific DNA
sites because different adduct conformations exist as inferred from NMR
structures of analogous CoBlm@DNA adducts. Specific drug interaction at
G-C/T sites involves complementary fit of the stable metal domain-linker
into the minor groove together with cooperative intercalation. Finally,
NO-Fe(II)Blm is used as an ESR probe of drug conformation in DNA adducts
at specific, non-specific, and single strand cleaved sites to reveal
whether the drug can bind in a productive manner. Supported by NIH
CA-22184.

**5. \'Fe^2+^ + O~2~\' is More Important than the Fenton Reaction in
Initiating Biological**

> **Radical Oxidation**
>
> Steven Y. QIAN§, and Garry R. BUETTNER‡ §Laboratory of Pharmacology &
> Chemistry, National Institute of Environmental Health Sciences,
> National Institutes of Health, P.O. Box 12233, Research Triangle Park,
> North Carolina, USA, 27709 ‡Free Radical Research Institute, The
> University of Iowa, Iowa City, Iowa, USA, 25542

\'Fe^2+^ + O~2~\' is More Important than the Fenton Reaction in
Initiating Biological Radical Oxidation.

Steven Y. QIAN§, and Garry R. BUETTNER‡ §Laboratory of Pharmacology &
Chemistry, National Institute of Environmental Health Sciences, National
Institutes of Health, P.O. Box 12233, Research Triangle Park, North
Carolina, USA, 27709 ‡Free Radical Research Institute, The University of
Iowa, Iowa City, Iowa, USA, 25542

Iron is well known to be an important initiator of biological free
radical oxidations, such as lipid peroxidation. Many iron-mediated
species have been proposed as the initiators for radical oxidation; but
the detailed mechanism is not clear. The mechanism that has been
generally accepted for iron\'s participation involved the Fenton or
iron-catalyzed Haber-Weiss reaction. However, an alternate mechanism has
been proposed that oxidations are initiated by iron in the form of
iron-oxygen complexes, i.e. perferryl or ferryl ions, based on the fact
that lipid peroxidation is not necessarily initiated by ·OH formed from
the Fenton reaction. Because of the high physiological ratio of
\[O~2~\]/\[H~2~O~2~\] (≈ 103), we hypothesize that the Fenton reaction
with pre-existing H~2~O~2~ is only a minor initiator of free radical
oxidations and that the major initiators of biological free radical
oxidations are the oxidizing species formed by the reaction of Fe^2+^
with dioxygen. To test our hypothesis, we have employed electron
paramagnetic resonance spin trapping to examine the free radical
oxidation of: 1) chemical (ethanol, dimethyl sulfoxide); 2) biochemical
(glucose, glyceraldehyde); and 3) cellular (L1210 murine leukemia cells)
subjected with an aerobic Fenton (Fe^2+^ + H~2~O~2~ + O~2~) or an
aerobic (Fe^2+^ + O~2~). As anticipated, the Fenton reaction initiates
radical formation in all the above targets. Without pre-existing
H~2~O~2~, however, Fe^2+^ and O~2~ also induce substantial target
radical formation. Under various experimental ratios of \[O~2~\]/\[
H~2~O~2~\] (1-100 with \[O~2~\] » 250 µM), we compared the radical yield
from the Fenton reaction vs. the radical yield from Fe^2+^ + O~2~
reactions. When \[O~2~\]/\[ H~2~O~2~\] \< 10, the Fenton reaction
dominates target molecule radical formation; however, production of
target-molecule radicals via the Fenton reaction is minor when
\[O~2~\]/\[ H~2~O~2~\] ≈ 100. Interestingly, when L1210 cells are the
oxidation targets, Fe^2+^ + O~2~ is observed to be responsible for
formation of nearly all of the cell-derived radicals detected, no matter
the ratio of \[O~2~\]/\[ H~2~O~2~\]. Our data demonstrate that when
\[O~2~\]/\[ H~2~O~2~\] ≈ 100, Fe^2+^ + O~2~ chemistry is an important
route to initiation of detrimental biological free radical oxidations.

**6. Oxidative Cleavage Of DNA Substrates Mediated By Copper Complexes
With**

> **Pyridyl(Alkyl)Amine Ligands**
>
> Kristi J. Humphreys^(a)^, Anne E. Johnson^(b)^, Steven E. Rokita^(b)^,
> and Kenneth D. Karlin^(a)^. ^(a)^Department of Chemistry, The Johns
> Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218;
> ^(b)^Department of Chemistry and Biochemistry, University of Maryland,
> College Park, MD 20742.

Copper complexes which oxidatively cleave DNA are believed to proceed
through copper(I)-derived intermediates that have yet to be
well-characterized. Given the large number and range of copper
pyridyl(alkyl)amine complexes in the literature for which the
copper(I)-dioxygen intermediates are known, we have undertaken to use
this background in investigating oxidation of biological substrates. To
this end, a series of Cu(II) compounds of varying nuclearity and
copper(I)-dioxygen reactivity have been studied with DNA substrates
(single-stranded and double-stranded oligonucleotides) in the presence
of or a reductant. The reactivity will be discussed with respect to
multinuclearity and complex-substrate interactions, including substrate
preference and sequence specificity.

**7. A Combinatorial Approach to the Discovery of New Metal Complexes
for**

> **Peptide Cleavage**
>
> Kathryn B. Grant\* and Sowmya Pattabhi. Department of Chemistry,
> Georgia State University, University Plaza, Atlanta, Georgia, USA,
> 30303-3083.

Metal ions and complexes which cleave proteins and small peptides under
nondenaturing conditions of temperature and pH hold great promise for
use in protein structural studies. However, the extreme stability of the
peptide amide bond has placed limits on the number of reagents
available. In addition, little is known about the rules that define
amino acid sequence specificity. We will present an overview of our
recent work aimed at the development of a new combinatorial approach for
the rapid identification of amino acid sequence motifs and metal
complexes for peptide cleavage. We have designed a positional scanning
peptide library for the analysis of copper and vanadium ions. Peptide
samples are treated \'on resin\' with metals and a fluorescamine-based
microplate assay is subsequently employed to identify cleaved peptide
sequences. We are now extending this approach toward the development of
a positional scanning peptide library that will be used to
simultaneously screen 8,000 tripeptides and a broad range of transition
metal complexes. We will also present a novel fluorescamine-based method
for monitoring the kinetics of metal-assisted peptide hydrolysis.
(\*Corresponding Author).

**8. Design of a Sequence-Specific Photonuclease from a Synthetic bZIP**

> **Metalloprotein**
>
> Robin C. Lasey^1^, Sunandita S. Banerji^2^, Michael Y. Ogawa^1^.
> ^1^Dept. of Chemistry and Center for Photochemical Sciences, Bowling
> Green State University, Bowling Green, Ohio, USA, 43403. ^2^Department
> of Biochemistry and Molecular Biology, Medical College of Ohio,
> Toledo, Ohio, USA, 43614.

The family of \'leucine zipper\' (bZIP) transcription factors comprises
an important class of oncoproteins in which the non-covalent
dimerization of independent peptide subunits creates a specific DNA
binding domain for the AP-1 sequence. The attachment of a photoactive
metal center to these peptides affords the possibility that they can be
used to target photodynamic therapy reagents to intracelluar targets of
choice. Thus, a synthetic bZIP peptide was prepared based on the basic
DNA-binding region of GCN4 and the coiled-coil region from a previously
prepared synthetic coiled-coil. A photoactive ruthenium site,
\[Ru(bpy)~2~(phen-IA)\], where IA = iodoacetate, was reacted with a
surface-exposed cysteine residue and the DNA-binding properties of the
resulting peptide were studied by electrophoretic mobility shift assays
using the consensus AP-1 sequence. The results show that the synthetic
bZIP peptide does recognize and bind the consensus AP-1 DNA element in a
site-specific manner. Emission lifetime measurments show that this
species has a lifetime of 1263 ns in argon-saturated aqueous solution.
However the lifetime decreases to 806 ns in air-saturated solution. The
free metal complex causes guanine-specific damage but the (GBR-CC)Ru
peptide is unable to cause photoinitiated DNA damage under conditions
where the peptide-DNA complex can be formed. We speculate that this
inability to cause DNA photodamage may be due to the site of metallation
of the peptide which places the ruthenium complex within the coiled-coil
region of the protein. Thus, ongoing work in our laboratory is
attempting to position the metal complexes closer to the site of DNA
binding, and to enhance the degree of metal-occupancy of these peptides.

**9. Inactivation of mRNA through Cleavage of the 5\'-cap Structure by
Metal Ion**

> **Complexes and Oligonucleotide Conjugates**
>
> Janet R. Morrow,\* Lara L. Chappell, Kevin P. McCue, Brenda F. Baker1
> and Danny Epstein. Department of Chemistry, State University of New
> York at Buffalo, Amherst, NY 14260 and 1Isis Pharmaceuticals, 2292
> Faraday Ave., Carlsbad, CA 92009.

The 5\'-cap of mRNA consists of an N7-methylated guanosine linked
through triphosphate to the 5\'-terminus of RNA. This structure is
important in processing of the mRNA transcript and is a potential target
in the control of gene expression through mRNA inactivation. We have
prepared both mononuclear and dinuclear metal ion complexes which
promote efficient cleavage of the 5\'-cap. Eu(III) macrocyclic complexes
with pendent alcohol groups promote 5\'-cap cleavage. Using
laser-induced luminescence spectroscopy we have shown that 5\'-cap
analogs bind to Eu(III) macrocyclic complexes with binding constants
ranging from 5900 to 44,000M^-1^. A single bound water molecule is
displaced upon binding to substrate. Several dinuclear metal ion
complexes and two metal ion combinations hydrolyze 5\'-cap analogs
efficiently, suggesting that two metal ions play a role in cooperatively
promoting cleavage. A Eu(III) macrocyclic complex-oligonucleotide
conjugate promotes a sequence-specific cleavage reaction at the 5\'-cap
structure of the ICAM-1 transcript. This conjugate efficiently inhibits
ICAM-1 protein expression in cells. From these studies, we have begun to
build an understanding of the interaction of metal ions with this
important substrate.

**Session 2. Metal Containing-Targets of Drug Action**

**10. Divalent Metal Binding and Mechanism of Action of the Methionine**

> **Aminopeptidases from Escherichia coli and Pyrococcus furiosus**
>
> Richard C. Holz\*, Ventris M. D\'souza, Shane S. Ruebush, Alicja J.
> Copik, and Brian Bennett. Department of Chemistry and Biochemistry,
> Utah State University, Logan, Utah 84322

In both eukaryotic and prokaryotic cells, methionyl aminopeptidases
(MetAP) selectively cleave methionine residues from the N-termini of
polypeptide chains \[1\]. Deletion of the gene encoding MetAP is lethal
to Escherichia coli and Salmonella typhimurium; therefore, MetAP\'s are
essential for cell growth and proliferation \[2\]. An important
physiologic role for MetAP\'s involves angiogenesis, the formation of
new blood vessels, which is essential for tumor growth. Recently, a
type-II MetAP from eukaryotes was identified as the molecular target for
the anti-angiogenesis drugs ovacilin and fumagillin as well as their
analog AGM-1470 \[3\]. Thus, the inhibition of aminopeptidase activity
in malignant tumors is critically important in preventing the growth and
proliferation of these types of cells. Based on these data, an
understanding of the structure/function relationship within native and
inhibited forms of MetAP is an important and necessary step towards the
rational design of potential chemotherapeutic agents.

MetAP\'s from E. coli, S. typhimurium, Pyrococcus furiosus, yeast,
porcine liver and humans have been identified and studied \[4\]. While
the identity of the metal ion in vivo is unknown, maximal activity was
demonstrated with Co(II) in each of these systems. We have re-examined
the activity levels of the MetAP from E. coli and Pyr. furiosus using a
modified HPLC method and found that under stringent anaerobic
conditions, Fe(II) provided MetAP enzymes with equal activity to the
Co(II) substituted enzymes while Mn(II) provided enzymes that retain
\~20 of the activity of either the Fe(II) or Co(II)-forms. Based on
these data, Fe(II) or Mn(II) is more likely the physiologically relevant
metal ion. Km values for the E. coli enzyme have been determined for the
substrate Met-Gly-Met-Met and were found to be 3.16 ± 0.34 mM for the
Co(II)-substituted form and 1.95 ± 0.74 mM for the Fe(II)-substituted
enzyme. Activity vs. equivalents of metal ion for both Fe(II) and Co(II)
added, indicated that maximal activity was obtained after the addition
of only one equivalent of metal ion. These data suggest that only one
metal ion is required for catalysis. The metal ion dissociation constant
Kd for the first metal binding site in the E. coli enzyme was found to
be 0.3 ± 0.2 microM and 0.2 ± 0.2 microM for Co(II) and Fe(II),
respectively. ICP and electronic absorption titration data indicated
that the second Co(II) ion is loosely bound. Concomitant with these
studies, we have probed the coordination environment of the Co(II)-,
Fe(II)-, and Mn(II)-loaded enzymes by a variety of spectroscopic methods
including electronic absorption, NMR, and EPR spectroscopies. Based on
these studies and previously reported X-ray crystallographic data \[4\],
a revised mechanism of action is proposed.

1\. Bradshaw, R.A., Brickey, W.W. and Walker, K.W. (1998) TIBS 23,
263-267.

2\. Taylor, A. (1996) in Molecular Biology Intelligence Unit (A., T.,
ed.), pp. 1-219, R. G. Landes Co., Austin, TX USA.

3\. Griffith, E.C., Su, Z., Niwayama, S., Ramsay, C.A., Chang, Y.-H. and
Liu, J.O. (1998) Proc. Natl. Acad. Sci. USA 95, 15183-15188.

4\. Lowther, W.T. and Matthews, B.W. (2000) Submitted to Protein
Structure and Function.

**11. Redox Regulation of Signal Transduction via Calcineurin**

> Tiffany A. Reiter, Robert T. Abraham, Mijin Choi, and Frank Rusnak.
> Dept of Biochemistry and Molecular Biology, Mayo Clinic & Foundation,
> Rochester, Minnesota, USA, 55905.

To explore whether the Ca^2+^/calmodulin-dependent protein phosphatase
calcineurin is subject to redox regulation in vivo, we used a luciferase
reporter gene construct whose expression was controlled by the
transcription factor NF-AT to monitor intracellular calcineurin activity
following redox state perturbations. The NF-AT reporter construct was
transfected into the T-cell Jurkat, and luciferase activity assessed
following treatment with phorbol ester and ionomycin in the presence of
either hydrogen peroxide or dithiothreitol. While dithiothreitol had no
effect, hydrogen peroxide completely abrogated NF-AT transactivation in
response to stimulation. The inhibitory effect was specific for NF-AT as
comparable levels of hydrogen peroxide had only minor effects on
constitutive transcription factors while an analogous construct under
AP-1 control showed a 5-fold stimulation in transactivation in the
presence of hydrogen peroxide. The inhibitory effect of hydrogen
peroxide was observed up to approximately three hours following mitogen
stimulation, a time point where NF-AT activity begins to increase under
normal conditions. Protein serine/threonine phosphatase activities from
Jurkat lysate indicated that calcineurin activity was inhibited not only
by hydrogen peroxide but also by high concentrations of dithiothreitol.
From these results we hypothesize that calcineurin phosphatase activity
is subject to redox regulation in vivo and are discussed in the context
of redox reactions involving active site metal ions.

**12. Mycobacterium tuberculosis Catalase/Peroxidase KatG in Isoniazid
Activation**

> **and Resistance**
>
> Frank Rusnak†\*, Nancy L. Wengenack\*, Smilja Todorovic§\*, James R.
> Uhl#‡, Nenad Jurani´c\*, Slobodan Macura\*, Franklyn R. Cockerill
> III#‡, and Bruce C. Kline\*, †Section of Hematology Research,
> \*Department of Biochemistry and Molecular Biology, #Division of
> Clinical Microbiology, ‡Division of Infectious Diseases, Mayo Clinic
> and Foundation, Rochester, Minnesota, USA, 55905; §Faculty of Physical
> Chemistry, University of Belgrade, Belgrade, Yugoslavia.

Mycobacterium tuberculosis KatG is a multifunctional heme enzyme
responsible for activation of the antibiotic isoniazid. A point mutation
in which serine at position 315 is mutated to threonine, KatG(S315T), is
found in \>50% of isoniazid-resistant clinical isolates. A comparison of
enzymatic activities for recombinant wild type KatG and KatG(S315T) have
demonstrated that KatG(S315T) is a competent catalase and peroxidase.
Spectroscopic characterizations of these two enzymes have indicated only
subtle and possibly insignificant differences in isoniazid binding,
suggesting that the S315T mutation does not alter the isoniazid binding
site. Isoniazid oxidation by KatG can proceed via two routes: a
peroxidative pathway requiring a hydroperoxide as oxidant, and a
cytochrome P450 oxygenase route which utilizes superoxide as oxidant.
Isoniazid oxidation via the peroxidative route occurs with the same rate
for both KatG and KatG(S315T), suggesting that this pathway is not
relevant for in vivo activation. KatG(S315T), however, is significantly
impaired in oxidizing isoniazid via the oxygenase pathway. These results
indicate an in vivo role for superoxide that correlates with isoniazid
susceptibility. These results are discussed in the context of the
mechanism of isoniazid activation and the molecular basis for resistance
afforded by the S315T mutation.

**13. Towards Understanding the Heme Environment Required for Activation
of**

> **Isoniazid by M. tuberculosis KatG**
>
> Kenton R. Rodgers and Gudrun S. Lukat-Rodgers Department of Chemistry,
> North Dakota State University, Fargo North Dakota 58105

KatG, the catalase peroxidase from Mycobacterium tuberculosis, is
important in the activation of the antitubercular drug, isoniazid (INH).
About 50% of INH-resistant clinical isolates contain the point mutation,
KatG(S315T). Comparison of the vibrational spectra of ferric KatG and
KatG(S315T) indicates that both proteins exist as a mixture of high-spin
and low-spin hemes at room temperature. While wild-type ferric KatG is
predominantly high-spin heme, ferric KatG(S315T) has a significant
six-coordinate low-spin heme population. Isoniazid binding to ferric
KatG and KatG(S315T) does not alter their spin state distribution at
room temperature. The heme pockets of KatG and KatG(S315T) are further
probed by characterization of their ferrous CO adducts. Three
vibrational modes, C-O and Fe-C stretching and Fe-CO bending, are
assigned using 12CO and 13CO isotope shifts. Two conformations are
observed for KatG-CO. Data for form I are consistent with a linear Fe-CO
unit perpendicular to the heme plane and a hydrogen-bonded proximal
histidine. The resonance Raman data for the second conformation, form
II, suggests a protonated proximal histidine and a slightly off axis CO
which is hydrogen bonded to a distal residue. Two conformations are also
observed for KatG(S315T)-CO. Its form I is quite similar to form I of
KatG. Its second conformation, form II, still has a tilted Fe-CO bond,
however, the distal hydrogen bonding is no longer present. This
disruption of distal hydrogen bonding in KatG(S315T) may account for its
inefficient activation of INH due to a destabilized oxy heme, the form
of the enzyme thought to be responsible for INH activation. Isoniazid
binding is detected in the resonance Raman signatures of the KatG and
KatG(S315T) CO adducts. The bent hydrogen-bonded CO of KatG-CO, form II,
is favored upon INH binding, further suggesting that distal H-bonding to
the exogenous ligand plays a role in INH activation by KatG.

**14. Proteolytic Activation of the Catalytic Activity of Purple Acid
Phosphatases: A**

> **Possible Regulatory Mechanism and Potential Therapeutic Target for
> Treatment of Osteoporosis and Other Disorders**
>
> B.A. Averill^1^, E.G. Funhoff^1^, Y.-L. Wang^2^, and G. Andersson^2^
>
> ^1^E.C.Slater Institute, University of Amsterdam, Plantage
> Muidergracht 12, NL 1018 TV Amsterdam, The Netherlands. ^2^ Karolinski
> Institute, Huddinge University, F46, 141 86 Huddinge, Sweden.

Purple acid phosphatase (PAP) is a metalloenzyme that catalyzes the
hydrolysis of monophosphate esters. In its active form, PAP contains a
binuclear, mixed-valent diiron center at the active site. In mammals,
PAP is present in tissues such as spleen, bone, skin, and heart, and is
localized in cells such as osteoclasts and dendritic cells. PAP is
believed to be involved in human diseases such as osteopetrosis,
Gaucher\'s disease and hairy cell leukemia, but its specific
physiological function(s) is (are) not yet known with certainty.

Mammalian PAPs are isolated as either intact or proteolytically cleaved
enzymes, each of which exhibits distinct kinetics and spectroscopic
characteristics. Compared to intact PAPs (e.g., uteroferrin, from
porcine uterine fluids), PAPs isolated in a proteolytically cleaved form
(e.g., bovine spleen PAP) have a ca. 4-5 x higher kcat, an increased pH
optimum, and a more rhombic EPR spectrum. The origin of these
differences has long been unclear. However, it has recently been shown
that proteases such as trypsin and the cathepsins are able to cleave
PAPs in an exposed loop of the polypeptide, producing a protein with
fragment masses of 16 and 20-22 kDa. Proteolytic cleavage is accompanied
by an increase in activity, a shift in pH optimum, and a change in EPR
spectrum, indicating a changing interaction between the diiron center
and the surrounding amino acids.

Based on characteristics of both the intact and cleaved forms of
recombinant human PAP and the recently published structure of
uteroferrin, a potential structural basis for the phenomenon of
activation has been identified. Through the interaction of Asp146, which
is located in an exposed loop domain near the active site, with either
His92 and/or the Fe^2+^ ligand Asn91, the nucleophilicity of the Fe^3+^
coordinated hydroxide is reduced and/or the electrophilicity of the
substrate is lowered in the intact protein. Proteolytic cleavage results
in the loss of these inhibitory interactions and consequently activates
the enzyme.

Using site-directed mutagenesis of recombinant rat PAP, we have been
able to study the interactions between Asp146 and the active site
residues to gain more knowledge about the mechanism of proteolytic
activation of PAPs. Whether such activation constitutes a
physiologically relevant regulatory mechanism, however, remains to be
proven.

**15. Nature\'s Way to Make Methane**

> S.W. Ragsdale, J. Telser, Y.-C. Horng, and B.M. Hoffman. Dept. of
> Biochemistry, Univ. of Nebraska, Lincoln, NE

Methanoarchaea are strict anaerobes that responsible for the synthesis
of one billion tons of methane per year. They are a key component of the
microbial flora in the human GI tract. To produce energy for growth, the
microbes synthesize CH4 from acetic acid, or H~2~/CO~2~, or even CO.
This poster will describe recent results on the initial and the ultimate
steps of methane synthesis from acetic acid. The initial step of
acetyl-CoA cleavage involves the bifunctional nickel enzyme CO
dehydrogenase/acetyl-CoA synthase (CODH/ACS). This enzyme catalyzes the
following reaction: acetyl-CoA -\> CO~2~ + CoA + methyl-X. CODH/ACS
accomplishes the coordinated generation and delivery of CO, an
energy-rich intermediate in this reaction, for the microbe that is toxic
to the host. The two subunits also coordinate electron flow, apparently
to stabilize a reactive intermediate generated during the reaction. The
ultimate step of methanogenesis is catalyzed by the nickel enzyme
methyl-Coenzyme M reductase (MCR), which catalyzes the following
reaction: methyl-SCoM + CoB-SH -\> methane + CoM-SS-CoB. The active
state of MCR is called red1, which is generated by reductive activation
of the so-called \'ox1\' state. Experiments using XAS; pulse radiolysis;
and EPR, ENDOR, and UV-visible spectroscopies, show that both the ox1
and red1 states are Ni(I). The role of coenzyme B (CoB-SH) has also been
clarified - it is intimately involved in the chemical step of methane
formation.

**16. The Evolving Mechanism of Metallo-beta-lactamase**

> Walter Fast, Zhigang Wang, Ann M. Valentine, Stephen J. Benkovic. The
> Pennsylvania State University, Department of Chemistry, University
> Park, PA

Widespread use of beta-lactam antibiotics provides incredible selective
pressures driving the evolution of resistance enzymes in bacteria.
Zinc-dependent beta-lactamases are emerging as a clinical threat and
represent a young class of developing enzymes that demonstrate
considerable structural and mechanistic differences. The less efficient
mono-zinc enzymes have a rate-limiting step preceding or concomitant
with C-N bond cleavage that requires protonation of the lactam nitrogen.
We have determined that the more efficient dinuclear zinc enzyme has a
rate-limiting step after C-N bond cleavage and does not require prior
N-protonation. Mutagenesis, pre-steady-state kinetics and a metal
chelator are used to probe the structural features responsible for the
observed rate acceleration and demonstrate both the tuning of
rate-limiting steps by a second shell zinc ligand and the true
co-catalytic nature of the dinuclear zinc site. Overall, features that
contribute 3.7 kcal/mol toward the C-N bond cleavage rate are elucidated
although some of the total acceleration is masked in the steady-state by
a change in rate-limiting step. These experiments illustrate one step in
the evolution of a catalytic mechanism and, in a larger perspective, one
step in the evolution of antibiotic resistance mechanisms.

**17. Structure and Chemistry of the Enzyme Active Site of Glyoxalase
I**

> Uwe Richter, Ph.D., National Institute of Standards and Technology,
> Center for Advanced Research in Biotechnology, Rockville, Maryland,
> USA, 20850.

The glyoxalase system, consisting of the two enzymes glyoxalase I and
glyoxalase II, represents the main factor in controlling the
concentration level of methylglyoxal in cells. It plays an important
role in the regulation of cell differentiation and proliferation.
Glyoxalase I catalyses the conversion of the thiohemiacetal, formed
nonenzymatically from methylglyoxal and glutathione, to
S-D-lactoylglutathione, which is then hydrolyzed by glyoxalase II to
D-lactic acid and glutathione. Modulation of the activity of the enzymes
may be related to both cancer and diabetes. Therefore, glyoxalase I has
been targeted for the development of novel anti-tumour, anti-protozoal
and anti-bacterial agents that by inhibition would raise methylglyoxal
concentrations to toxic levels.

Our work is aimed to provide detailed information about substrate and
product binding in the active site of glyoxalase I, which is essential
for a truly rational design of competitive inhibitors. Starting from the
x-ray structure of an inhibitor/enzyme complex reactant and product
complexes are constructed and optimized. The optimizations are carried
out at the ab initio SCF level combined with the newly developed
effective fragment potential methodolgy (EFP). This methodology is
capable of reproducing experimental active site structures introducing
only minor constraints in the quantum system. This is shown for an
inhibitor/enzyme complex. We also present a calculated structure for a
reactant/enzyme complex, which cannot be obtained experimentally and
which gives new insight concerning the initial step of the glyoxalase I
reaction.

**18. Engineering Type-1 Copper Centres In Redox Enzymes For Hot
Wiring**

> Martin Ph. Verbeet#, Lars J.C. Jeuken#, Hein J. Wijma#, Maria
> Fittipaldi\*, Martin J. Boulanger§, Martina Huber\*, Michael E.P.
> Murphy§, and Gerard W. Canters# #Leiden Institute of Chemistry,
> Gorlaeus Labs,:\*Dept. of Molecular Physics, Huygens Lab., Leiden
> University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands, §
> University of British Columbia, Vancouver,
> Canada.Verbeet@chem.leidenuniv.nl

The type-1 Cu centre is the electron transfer site found both in
single-domain cupredoxins like azurin and in multi-copper domain enzymes
like nitrite reductase and ceruloplasmin. Such a centre can also be
considered as a module that is capable of mediating electrons in an
amperometric device for the sensing of small chemicals, e.g., nitrite. A
major challenge for such a device lies in the stability of the enzyme
coating on the electrode and the efficiency of electron transfer from
enzyme to electrode. To resolve this, direct insertion, i.e., hot
wiring, by means of a linker directly coordinated by the copper of the
type-1 site and on the other end connected to the electrode, could be
adventageous.

To obtain a type-1 site accessible for external ligands we have shown
that the replacement of the surface-exposed, Cu-coordinating His-residue
by a Gly or Ala is sufficient. When external Cu ligands are added, the
spectral properties of the mutant type-1 site are restored to wild type
. Recently, the functionality for such a mutant, i.e., His-117 Gly
azurin, could be electrchemically determined: the redox potential scheme
for the imidazole ligand shows an Em (vs NHE) \~ 400 mV which is
significantly closer to the wild type Em (310 mV) than the Em the for
the chloride ligand .

For hot wiring to a sensing redox-enzyme we introduced the same type-1
mutants into the copper-enzyme nitrite reductase (NIR) from Alcaligenes
faecalis S6. In this trimeric NIR molecule one copper site is a typical
type-1 redox site, the other a type-2 catalytic site. The UV-visible and
EPR spectra show that it is possible to reconstitute the type-1 site in
NIR His-145 Ala/Gly by external ligands like imidazole. The UV-visible
spectrum of the His-145 Ala mutant with imidazole reminds of the typical
blue copper sites and differs from the greenish wild type and His-145
Gly NIR spectrum.

1Den Blaauwen, T. and Canters, G.W., ., Creation of type-1 and type-2
copper sites by addition of exogenous ligands to the Pseudomonas
aeruginosa azurin His117Gly mutants. 1993, J. Am. Chem. Soc.115,
1121-1129 J.Am.Chem. Soc. 1993, 115, 1121-29.

Jeuken, L.J.C., Van Vliet, P., Verbeet, M. Ph., Acosta, R.C., McEvoy,
J., Armstrong, F.A., Canters, G.W., Role of the surface-exposed and
copper-coordinating histidine in the blue copper protein azurin:
electrochemical evaluation of His117Gly azurin. (submitted)

**19. Identifying And Designing Of Calcium-Binding Proteins.**

> Jenny J. Yang\*^1^, Wei Yang^1^, Hsiau-wei Lee^1^, Yiming Ye^1^,
> Zhi-ren Liu^2^, Homme Hellinga^3^. ^1^Department of Chemistry, Georgia
> State University, ^2^Department of Animal Science, Auburn University,
> ^3^Department of Biochemistry, Medical Center,Duke University

Designing calcium-binding sites in non-calcium-binding proteins will
deepen our understanding of the key determinants for calcium binding
affinity, calcium-conducted conformational change, and brings us closer
to the design of novel proteins with desired functions. We have
demonstrated that natural calcium-binding sites in calmodulin,
parvalbumin and calbindinD9K can be identified and searched back using
the parameters from the geometry of an ideal pentagonal bipyramid with a
computer algorithm. The identified natural sites in EF proteins have the
smallest deviation from the defined geometry. Our work indicates that a
method for searching calcium-binding sites in proteins has been
established. To test the feasibility of using a beta-sheet protein frame
as a host system for design of a calcium-binding site with pentagonal
bipyramidal geometry, we have carried out intensive exercises on
designing calcium-binding sites in Domain 1 of CD2. After rigorous
evolutions of sidechain packing and the protein environment, several
calcium-binding sites have been successfully engineered into the host
protein with calcium binding ability.

20. **The Guanidine Moiety as a Ligand for Hemin**

> Dabney W. Dixon\* and Min Sook Kim; Department of Chemistry, Georgia
> State University, Atlanta, GA 30303

The potential interaction of hemes with compound bearing guanidino
moieties are of current interest in conjunction with studies of
guanidine-induced heme protein unfolding, arginine derivatives as heme
protein substrates and aminotriazoles as mechanism-based inhibitors for
some heme proteins. We have used H-1 NMR to characterize the binding of
guanidyl ligands to hemin dimethyl ester, Fe(III)PPIXDME. The low-spin
complexes were obtained in Me~2~SO-d~6~ with cyanide as the opposing
axial ligand. Guanidine-containing ligands included ethylguanidinium
sulfate, N,N,N\',N\'-tetramethylguanidine, 2-aminoimidazole and
1-methyl-2-aminoimidazole as well as guanidine itself. L-arginine gave
two sets of four resonances each for the heme methyl groups. These were
assigned as the diastereomers of the mono-arginine, monocyano complex
with binding of the arginine through the amino nitrogen.

**21. Nitric Oxide Dioxygenases: Efficient Catalysts for Nitric Oxide
Metabolism in**

> **Microbes and Mammals**
>
> Paul R. Gardner, Children\'s Hospital Medical Center, Cincinnati, OH
> 45229

Escherichia coli and other microbes produce flavohemoglobins (flavoHbs)
with nitric oxide dioxygenase (NOD) activity. The enzyme protects
microbes from the antibiotic effects of nitric oxide (NO) by converting
NO and ferrous-O~2~ to nitrate. NOD steady-state and transient kinetics
demonstrate an efficient dioxygenase mechanism and function for flavoHb
and suggest a similar function for members of the widely-distributed Hb
family. Kinetic and structural differences are noted for the modern
mammalian O~2~ transport and storage Hbs which may preclude an efficient
enzymatic NOD activity. Mechanistic inhibitors of NOD activity include
CO, NO, cyanide, azide, phenylhydrazines, and the flavoenzyme inhibitor
diphenylene iodonium. Mammalian cells express a NO consuming NOD
activity with similar steady-state kinetics and inhibitor sensitivities.
The mammalian activity protects cells from NO toxicity, and may also
serve as the O~2~-modulated transducer for NO signaling capable of
matching O~2~ delivery (arteriole blood flow) to regional O2 demands.
Comparative kinetic, mechanistic, structural and functional studies of
NODs and Hbs promise to yield insights for antibiotic, cardiovascular,
and anti-tumor drug design.

**Session 3. Imaging, Radiology, and Photodynamic Therapy**

**22. Receptor Based Biosensor for Gallium Using Novel Therapeutic**

> **Immunoconjugate**
>
> Omowunmi A. Sadik. Dept. of Chemistry, SUNY Binghamton, New York, USA,
> 13902.

Metals and radionuclides are usually incorporated with coupled protein
reagents for in vivo diagnosis of diseases. Numerous radiometals have
been introduced via suitable strongly coordinating ligands. However, the
demand for bifunctionality limits the application of these ligands. A
new chelate-based protein conjugate has been synthesized using
pyridylazo phenols, naphthols and resorcinol (PAR). The PAR ligands were
coupled to bovine serum albumin (BSA), ovalbumin (OVA) and alkaline
phosphatase (AP). The resulting PAR conjugate was used to detect gallium
in biological matrices using a non-antibody-based immunochemical assay
format. PAR-OVA and PAR-AP conjugates were used as capture and detector
chelators respectively, resulting in a detection limit of 5 x 10^-8^ M,
and a remarkable selectivity for gallium (III) relative to other metals
considered. Gallium plays a very important role in the diagnosis of
tumor and for possible treatment of malignancies. The use of novel
bioconjugates for achieving antibody-type specificity for quantitative
characterization of gallium can serve as a model for therapeutic agents,
tumor imaging reagents and other applications. In this presentation, the
design, characterization and testing of these conjugates will be
discussed.

**23. Synthesis and Relaxometric Investigations of Starburst
Dendrimer-DOTA-M**

> **(M=Gd(III), Mn(II), Fe(III))**
>
> L. H. Bryant, Jr.^1^, M. W. Brechbiel^2^, J. W. M. Bulte^1^, C. Wu^2^,
> V. Herynek^3^, J. A. Frank^1^. ^1^Laboratory of Diagnostic Radiology
> Research, ^2^Radiation Oncology Branch, ^3^Neuroimaging Branch,
> National Institutes of Health, Bethesda, MD 20892

Starburst‚ polyamidoamine (PAMAM) dendrimers have uniform surface
chemistry and minimal molecular weight distribution and shape variation.
The uniform surface chemistry allows for reproducible chemical
derivatization. We have covalently attached derivatized macrocyclic
chelates to the surface of the generation 7 and 9 dendrimers. The
appropriate metal ions useful as magnetic resonance imaging (MRI) agents
such as gadolinium, manganese and iron were coordinated to the
dendrimer-based macrocyclic chelates. We have been able to synthesize
the largest number of metal ions per macromolecule (i.e., dendrimer)
that has ever been reported. The relaxometric investigations, which is a
measure of the relation rates per mM concentration of metal ion as a
function of magnetic field strength, shows that at the clinically
relevant field strength of 1.5 T, the dendrimer-based gadolinium
chelates are about a factor of four more efficient than the clinically
used monomeric gadolinium chelates. We have explored the potential of
the new dendrimer-based gadolinium chelates for use in MR angiography.
Delineated vascular visualization, in the rat, was observed for up to at
least one hour. These results demonstrate the potential of these
dendrimer-based chelates for use as MR contrast agents.

**24. Lung Cancer - From Radiodiagnosis to Radiotherapy with Novel
Somatostatin**

> **Receptor-Binding Peptides**
>
> Rajeesh Manchanda. Diatide, Inc., Londonderry, New Hampshire, USA,
> 03053.

Somatostatin-receptors (SSTRs) are normally overexpressed on tumor
cells. Small synthetic peptides that show high affinity and specificity
to SSTRs can be employed to diagnose and treat tumors. Tc 99m
Depreotide, a cyclic peptide coupled to technetium-99m via a chelator
was shown to localize on tumor masses in vivo. Tc 99m depreotide
(NeoTectTM) has been shown to be effective and safe in humans. For
therapy, depreotide was chelated to rhenium-188, a beta-emitter
(beta-61538;max- = 2.1 MeV, 17 h half-life). Re-188 depreotide showed in
vivo uptake in rat pancreatic tumor (AR42J)-xenografts in nude mice and
with a repeat dose regimen, exhibited a dose-responsive tumor growth
inhibition in this model of a SSTR-expressing tumor. However, slow renal
clearance resulted in nephritis and myelosuppression. To overcome these
adverse effects, P2045, an analog of depreotide, was selected as the
second-generation candidate for radiotherapy. Indeed, Re-188 P2045
showed higher tumor uptake and faster renal clearance than Re-188
depreotide in AR42J tumor-xenograft nude mice. In this model, a
repeat-dose regimen of Re-188 P2045 afforded a dose-responsive tumor
growth inhibition with no adverse effects. Thus, SSTR-specific peptides
coupled to two different radioisotopes may now be applied not only for
diagnosis but potentially also for management of lung cancer. Detailed
experimental plans, scintigraphic images, data tables, histopathological
results and tumor growth inhibition graphs will be presented.

**25. MR Tracking of Cell Migration and Myelination Following
Transplantation of**

> **Magtagged Glial Cells**
>
> J.W.M. Bulte, S.-C. Zhang, P. van Gelderen, V. Herynek, E.K. Jordan,
> I.D. Duncan, J.A. Frank. National Institutes of Health and University
> of Wisconsin.

OBJECTIVE: Transplanted glial cells and their precursor cells can
(re)myelinate axons, raising the possibility of therapeutic intervention
in myelin disorders. We have tagged grafted cells with a magnetic label
in order to track their migratory capacity and induced myelination
non-invasively using high resolution MR imaging.

METHODS: Iron oxide nanoparticles were shuttled into cells using a
covalently linked anti-transferrin antibody construct. Approx. 5E4
MagTagged viable (n=5), MagTagged paraformaldehyde-killed (control,
n=2), and untagged (control, n=5) cells were grafted in the spinal cord
of neonatal myelin-deficient (md) rats. At either 10 (n=4) or 14 (n=8)
days following transplantation, spinal cords were removed and imaged at
78 µicron isotropic resolution

RESULTS: The 3D images showed extensive migration (up to 8.4 mm) of
grafted cells, in particular in the area of the dorsal column. No
spreading of contrast could be observed in the control graft MR images.
Histopathological correlation showed an excellent agreement between the
observed MR contrast and areas of Prussian Blue- and myelin-positive
staining.

CONCLUSIONS: MagTagged glial cells fully retain their migration- and
myelinating capacitiy in vivo. MR tracking of neurotransplanted cells
appears feasible, and may be used to accurately map the achieved extent
of (re)myelination.

**26. Seeing is Believing: Visualizing In Vivo Gene Expression and
Secondary**

> **Messengers by Magnetic Resonance Imaging**
>
> Thomas J. Meade. Division of Biology and the Beckman Institute,
> California Institute of Technology, Pasadena, California, USA, 91125

MRI offers a non-invasive means to map brain structure and function by
sampling the amount, flow or environment of water protons in vivo. Such
intrinsic contrast can be augmented by the use of paramagnetic contrast
agents in both clinical and experimental settings; however, these agents
are little more than anatomical reporters which can at best label
individual fluid compartments or distinguish tissues that are
magnetically similar but histologically distinct. To permit a more
direct imaging of the physiological state of cells or organs, we have
prepared and tested several new classes of \'smart\' MRI contrast agents
that change their influence on nearby water protons in a conditional
fashion. The agents modulate fast water exchange with the paramagnetic
center, yielding distinct \'strong\' and \'weak\' relaxivity states. The
modualtion is triggered by two types of biological events: i. enzymatic
processing of the agent and, ii. binding of an intracelluar messenger.
These agents represent the first examples of direct, three dimensional
visualization of gene expression and intracellular second messenger
concentration in the form of a 3D MR image.

**27. The First Three-Dimensional Perfluorinated Phthalocyanine:
Synthesis,**

> **Structure and Photodynamic Activity**
>
> B.A. Bench^1^, A.C. Beveridge^1^, I.G. Calasso^1^, G.J. Diebold^1^, J.
> Van Lier^2^, S.M. Gorun^1^. ^1^Department of Chemistry, Brown
> University, Providence, Rhode Island, 02912 USA ^2^Department of
> Nuclear Medicine and Radiobiology, University of Sherbrooke
> Sherbrooke, Quebec, Canada

Phthalocyanines may be used for \'photodynamic therapy\' (PDT), a
process in which a light activated sensitizer produces singlet oxygen to
cause destruction of tumor cells. Because resistance to self-oxidation
of currently used porphyrin-based photosensitizers is an issue, we
present here the first three-dimensional (bulky) phthalocyanines-based
sensitizer that lacks C-H bonds. The built-in steric hindrance offers
the additional advantage of minimizing self-aggregation. The first
examples of non-planar perfluorinated phthalonitriles have been recently
reported. (J. Fluor. Chem., 1998, 91, 37) The 3,4 disubstituted
phthalonitrile isomer has been used to prepare zinc octakis
(perfluoroisopropyl) perfluorophthalocyanine, F64PcZn (R1 = i-C3F7,
perfluoro isopropyl, R2 = F) as a single isomer. Unlike the planar
H16PcZn, (R1 = R2 =H), F64PcZn does not aggregate and produces
effectively singlet oxygen, as measured by the photoproduction of
L-tryptophan hydroperoxide. While F64PcZn showed little cytotoxic effect
in vitro, it was highly phototoxic in vivo. Using only 50 % of the dose
of F16PcZn, (R1 = R2 =F), F64PcZn showed less oedema with complete
necrosis of mice mammary tumor cells. Measurements of triplet-state
lifetimes were performed using a transient grating technique. In
comparison with H16PcZn (lifetime \< 1 microsecond), the triplet-state
lifetime of F64PcZn is about 50 microseconds, which is consistent with
the results obtained in vivo.

**28. Metalloenediynes For Thermal And Photochemical Control Of
Bergman**

> **Cyclization**
>
> Pedro J. Benites, Diwan Rawat, and Jeffrey M. Zaleski. Department of
> Chemistry, Indiana University, Bloomington, IN 47405

The enediyne antitumor antibiotics possess the unusual
(Z)-1,5-diyne-3-ene unit that rearranges in the presence of biological
reducing equivalents to form a potent 1,4-phenyl diradical intermediate,
which performs double H-atom abstraction from cellular DNA. Since their
discovery, studies of biomimetic enediynes have shown that several
factors influence the kinetics and thermodynamics of enediyne
cyclization. Among these are the distance between the alkyne termini, as
well as the redox state and electronic structure of the adjacent
chromophore. In addition, enediynes are also known to be unstable to
ground state oxidation and reduction, and are susceptible to photo- and
photoredox activation. The inherent structural, electrochemical, and
photochemical properties of metal ions make them outstanding activators
for the cyclization of enediyne ligands. We have prepared various
metal-binding enediynes and their corresponding Cu(I) and Cu(II)
complexes, as well as those of other transition metals. The structures
and thermal reactivities of these complexes, as well as their
photoinduced DNA-cleaving capabilities will be presented.

**Session 4. Metal Metabolism as a Therapeutic Target**

**29. Synaptic Release of Free Zinc Ions in the Brain: Roles in Brain
Function,**

> **Disease, and Injury**
>
> Frederickson^1^ CJ, Suh^1^, SW, McAdoo^1^, DJ, Bush^2^, AI
> Thompson^3^, RB, Whetsell^4^, WO, Fierke^5^, CA, Hough^6^, C,
> Sarvey^6^, J., and Danscher^7^, G. (1) The University of Texas medical
> Branch, Galveston TX, (2) Harvard Medical School, Boston, MA, (3) The
> University of Maryland Baltimore Medical School, Baltimore, MD, (4)
> Vanderbilt Medical School, Nashville, TN, (5) The University of
> Michigan, Ann Arbor, MI, (6) The Uniform Services Medical School,
> Bethesda, MD. (7) The University of Aarhus, Aarhus, DK.

Neurons that sequester zinc in their pre-synaptic vesicles and release
the ions during physiological activity form a major component of the
neuronal circuitry of the mammalian cerebral cortex. Co-released with
glutamate, the zinc is known to provide a potent modulation of the
glutamatergic receptor function, predominantly as a feed-forward
down-regulator of excitatory amino acid responsiveness.

We have explored the roles of synaptically released zinc in epileptic
disorders, Alzheimer\'s disease, and in the excitotoxic contexts of
ischemia , blunt trauma (cord and cerebrum) , and seizures. Our data
(along with others\') suggest that the release of pathologically-high
levels of Zn^2+^ is a contributing cause of neuron injury and death in
all three models of excitotoxicity, and perhaps in Alzheimer\'s disease
as well.

We are currently exploiting genetically-engineered variants of native
zinc-containing proteins to develop tools for monitoring and for
buffering intracranial free zinc levels. Detection and control of excess
Zn^2+^ may be a powerful approach for preventing neuron death in the
acutely-head and brain injured patient. Supported by NINDS RO1 to RBT
and CJF; NINDS SBIR to CJF; NINDS RO1 to WOW; Danish Res. Council to GD.

**30. Fluorescent Peptidyl Platforms for Metal Ion Sensing in Aqueous
Solution**

> Dierdre A. Pearce. Dept of Chemistry, Massachusetts Institute of
> Technology, Cambridge, MA, USA.

The design of chemosensors for analysis of trace metal ion species in
biological solutions is a particularly challenging problem. We have
chosen peptidyl architecture to build such chemosensors because its
modular nature provides the means to \'tune\' the selectivity and
sensitivity of a sensor for a particular metal ion by modulating the
peptide secondary structure and incorporating ligating natural and
non-natural amino acids into relevant sites of the peptide sequence.
Such sequences are readily prepared by solid phase synthesis techniques
and are labeled with a fluorophore having appropriate photo-physical
properties. Moreover, peptide chemistry is compatible with chemical and
biological methodologies developed for generation and screening of
libraries of potential metal binding sequences. Sensors developed using
these strategies are capable of detecting trace metal ions in aqueous
solution over a wide dynamic range (nM to mM).

**31. The Shu S protein of Shigella dysenteriae is a Heme-Sequestering
Protein that**

> **Binds and Protects DNA**
>
> Angela Wilks and John Baumgartner, Dept. of Pharmaceutical Sciences,
> University of Maryland, Baltimore, Maryland, USA, 21201-1180.

The ability to transport and utilize heme as an iron source by Shigella
dysenteriae is dependent on the iron-regulated expression of a number of
genes including the outer-membrane receptor ShuA and the cytoplasmic
protein ShuS. The ShuS protein has no sequence homology with any other
known proteins and its role in heme acquisition has not previously been
determined. The protein has been expressed in Escherichia coli at high
levels as a soluble protein with an estimated molecular weight on
SDS-PAGE of 37 kDa. The purified protein forms a 1:1 complex with heme
and has a hemeprotein spectra similar in nature to the cytochromes in
which both ligands to the heme come from amino acid residues on the
protein. In addition the ShuS protein was shown to non-specifically bind
double stranded DNA in the presence or absence of heme. It appears
therefore, that ShuS functions as both a heme storage protein, during
periods of active heme transport,

and as a DNA binding protein to protect the DNA from any ensuing heme
mediated oxidative damage. In this respect the protein is functionally
similar to the prokaryotic Dps DNA binding proteins which act to
sequester and protect DNA during periods of starvation or oxidative
stress.

**32. Accelerating Iron Release from Transferrin**

> Wesley R. Harris, Department of Chemistry, University of Missouri-St.
> Louis, St. Louis, MO 63121.

The rate at which low molecular weight ligands are able to remove iron
from serum transferrin often appears be limited by a slow conformational
change in the protein that restricts access of the chelating agent to
the protein-bound ferric ion. However, some ligands, e.g. pyrophosphate,
are able to avoid this limitation by exhibiting a kinetic component for
iron removal that is first-order in ligand. Our hypothesis has been that
these ligands are able to gain access to the iron by first substituting
for the synergistic carbonate anion in the ferric-transferrin complex. A
series of small ligands have been tested to determine what other ligand
types can mediate the transfer of iron from serum transferrin to
desferrioxamine B. Phosphonoformic acid and phosphonoacetic acid are
almost as effective as pyrophosphate itself. Diphosphonates,
hydroxyphosphonates and

hydroxycarboxylate ligands are less effective. A more complete kinetic
analysis of iron removal by the phosphonocarboxylate ligands is underway
to determine whether they will also show the first-order component for
iron removal.

**33. Fe(III) Coordination and Redox Properties of a Bacterial
Transferrin**

> A. L. Crumbliss^(a)^, C. H. Taboy^(a)^, K. G. Vaughan^(b)^, T. A.
> Mietzner^(b)^ and P. Aisen^(c)^. (a) Dept. of Chem., Duke University,
> Durham, NC 27708; (b) Dept. of Mol. Genetics & Biochem., Univ. of
> Pittsburgh School of Medicine, Pittsburgh, PA 15261; (c) Dept of Phys.
> & Biophys., Albert Einstein College of Medicine, Bronx, NY 10461.

Ferric binding protein is a periplasmic iron transport protein that
occurs in many pathogenic bacteria. This protein functions in a similar
manner to that of the transferrins by binding and transporting Fe(III)
between the inner and outer membrane of gram negative bacteria. A recent
crystal structure of ferric binding protein derived from Haemophilus
influenzae shows a single Fe(III) binding site with protein side chains
(tyr, tyr, glu, his) occupying four coordination sites and exogenous
PO43- and H2O completing the inner coordination shell.1 The similarities
and differences in binding site compared with human transferrin is of
interest, particularly with respect to the mechanism for Fe capture and
release. We have characterized the Fe(III) binding site of ferric
binding protein derived from Neisseria gonorrhoreae by measuring the
Fe3+ affinity constant at pH 6.5 in the presence of PO43-, the EPR
spectra for recombinant Fe3+nFbp in the presence of PO43- and HCO3-, the
P-31 NMR spectrum of the apo and holo protein, and the Fe(III/II) redox
potential. From these data we are able to estimate the apo protein\'s
affinity constant for Fe2+ at pH 6.5 in the presence of PO43-,
conditions which approximate those of the periplasmic space. These
studies address the molecular mechanism for Fe transport in pathogenic
bacteria and whether redox may play a role in the process.

1\) C. M. Bruns, A. J. Nowalk, A. S. Arvail, M. A. McTigue, K. G.
Vaughan, T. A. Mietzner, and D. E. McRee, Nature Structural Biology,
1997, 4 (11), 919.

**34. Ferritin Is A Nuclear Protein That Responds To Cell Stress And
Protects DNA**

> K.Thompson, M.G. Fried†, Z. Ye, and J.R. Connor. Department of
> Neuroscience and Anatomy, †Department of Biochemistry and Molecular
> Biology. The Pennsylvania State University, Hershey, PA 17033

The cytoplasmic iron storage protein ferritin has been recently
described as a transiently expressed protein in select cell nuclei.
Within nuclei, ferritin\'s function may involve both DNA protection and
DNA damage. We found ferritin is present in neuronal nuclei in both
humans and rodents at early post-natal periods but is predominantly
cytoplasmic in the adult. In adult mice, ferritin can be induced to
return to neuronal nuclei by hypoxic ischemic insult indicating
selective cell expression and suggesting a protective role. We
established a cell culture model to determine the mechanism and
consequence of ferritin nuclear translocation using human astrocytoma
cells. Ferritin\'s presence in the nucleus increases by increasing
cellular iron levels and through exposure to hydrogen peroxide and
cytokines indicating cell stress as a factor in inducing ferritin
movement into the nucleus. In vitro extracellular uptake studies reveal
that H-ferritin is selectively taken up into the nucleus, whereas
extracellular L-ferritin remains cytoplasmic. Nuclear translocation of
ferritin is blocked by wheat germ agglutinin, ATP depletion, and
incubation at 4°C indicating entry through an active nuclear pore.
Cycloheximide treatment decreased ferritin nuclear levels indicating
that the presence of ferritin in the nucleus is post-transcriptionally
regulated and requires de novo synthesis. Cells in which ferritin is
removed from the nucleus and translocation blocked with WGA are
susceptible to hydrogen peroxide induced DNA damage. Supercoil
relaxation assays found H-ferritin protects DNA better than other weak
iron binding proteins. In conclusion, this study presents evidence for
the novel findings that localization of ferritin to cell nuclei is
ferritin subunit specific, post-transcriptionally regulated, actively
transported into the nucleus through nuclear pore complexes in vitro,
and protects DNA. These data expand the function of ferritin and suggest
ferritin nuclear localization is a well-regulated cellular event that
responds to cell stresses and protects DNA from oxidative damage.

**35. Investigation of Structure and Metal Binding Properties of
Transferrins by**

> **Electropray MS**
>
> D.Gumerov, I.Kaltashov, Department of Chemistry, University of
> Massachusetts, Amherst, MA 01003.

We are using several parallel mass spectrometry based strategies to
study conformational and metal binding properties of the N-lobe of human
serum transferrin (TfN). Stability of a protein-ferric ion-synergistic
anion complex is monitored under native and mildly denaturing conditions
using ESI MS. H/D exchange reactions are employed to probe
conformational stability of both apo- and holo-forms of the protein. We
are also evaluating utility of gas phase protein ion fragmentation for
structural characterization of transferrins using FTMS. Iron release
from the protein and conformational changes triggered by lowering
solution pH and/or addition of iron chelating agents are investigated by
monitoring mass shift and changes in charge state distributions of
protein ions. Conformational stability of TfN and some of its variants
is also studied by H/D exchange reactions under native and near-native
conditions.

Our titration studies have indicated that in the absence of
non-synergistic anions the transition between the \'closed\' (holo) and
\'open\' (apo) conformations most likely occur

through a partially unfolded state of the protein. Addition of ammonium
citrate to the system changes the mechanism of iron removal from the
protein (no partially unfolded proteins have been detected) and results
in significant facilitation of the dissociation process.

**36. Why is lead toxic? Unraveling the Molecular Mechanism(s) of Lead
Poisoning**

> Hilary A. Godwin,†‡ Elizabeth S. Claudio,† Sandhya Deo, † Cameron E.
> Forde,† Ricardo A. Garcia,†‡ John C. Payne,† Brian Rous†. Department
> of Chemistry and Department of Biochemistry, Molecular Biology, and
> Cell Biology, Northwestern University

Lead Poisoning is the most common environmentally caused disease in the
United States, affecting 4-5% of children nationwide. Despite this, the
molecular basis for lead\'s toxicity has not been widely investigated.
In the past, studies on the fundamental biological chemistry of Pb^2+^
have been stymied by the widespread misconceptions that lead is
spectroscopically silent and kinetically inert. Our goal has been to
develop spectroscopic techniques to probe lead speciation and to use
these techniques to investigate the interactions between Pb^2+^ and
protein targets. Towards this end, we have developed absorption,
fluorescence, and nuclear magnetic resonance techniques for
investigating lead-protein interactions. We have used these
methodologies to investigate the interactions between lead and proteins
that play important roles in neurological signaling and development. The
proteins that we have investigated to date naturally bind either calcium
(e.g. synaptotagmin) or zinc (e.g. structural zinc-binding domains and
aminolevulnic acid dehydratase). These studies reveal that lead can
compete effectively with calcium and zinc for binding sites in proteins,
but that lead has a much higher affinity for cysteine-rich zinc sites
than it has for calcium sites. Furthermore, these studies revel that
lead can be kinetically labile even when it is tightly bound. These
insights into the biological chemistry of lead have helped to pinpoint a
new class of potential targets for lead, members of the steroid receptor
superfamily. We are currently testing the ability of lead to target this
important class of proteins both in vitro and in vivo. In addition, we
are using these insights to rationally design fluorescent sensors and
improved chelating agents for lead.

References:

1\. \'Lead-Fingers: Pb(II)-Binding to Structural Zinc-Binding Domains
Determined Directly By Monitoring Lead-Thiolate Charge Transfer Bands\'
Payne, J. C.; ter Horst, M. A.; Godwin, H. A. J. Am. Chem. Soc. 1999,
121, 6850-6855.

2\. \'A Selective, Ratiometric, Fluorescent Sensor for Pb2+\' Deo, S.;
Godwin, H. A. J. Am. Chem. Soc. 2000, 122, 174-175

3\. \'207Pb-1H Two-Dimensional NMR Spectroscopy: A Useful New Tool For
Probing Lead(II) Coordination Chemistry\' Claudio, E. S.; ter Horst, M.
A.; Forde, C. E.; Stern, C.; Zart, M. K.; Godwin, H. A. Inorg. Chem.
2000, 39, 1391-1397.

4\. \'Calcium Triggers An Intramolecular Association Between The C2
Domains Of Synaptotagmin\' Garcia, R. A.; Forde, C. A.; Godwin, H. A.
Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 5883-5888.

**37. Lead-Filled Tetraplex: Solution and Solid State Studies of
G-Quartets Bound to**

**Pb^+2^**

> Frank Kotch, James C. Fettinger and Jeffery T. Davis\*. Department of
> Chemistry and Biochemistry, University of Maryland, College Park, MD
> 20742

In addition to an affinity for Na^+^ and K^+^, G-quartets also bind
divalent cations. Earlier this year, Shafer reported that Pb^+2^ is more
potent than K+ at inducing G-quartet formation in the thrombin-binding
aptamer.1 Since Pb^+2^ (1.21 Å) and K^+^ (1.33 Å) are similar in size
and in coordination properties it is reasonable that Pb^+2^ would
stabilize G-quartets

Motivation for studying Pb^+2^ binding to natural products is driven by
a desire to understand the molecular basis for lead\'s toxicity.
Identifying new structural motifs that selectivity coordinate Pb^+2^ may
accelerate the development of therapeutics to combat lead poisoning.
While lead\'s coordination chemistry is well understood, there are few
details regarding how Pb^+2^ binds to specific sites in biomolecules. In
proteins, Pb^+2^ prefers to coordinate to carboxylate and thiol
sidechains. X-Ray crystallography has shown that tRNA and RNA leadzymes
have specific Pb^+2^ binding sites.2,3 Motivated by Shafer\'s discovery
that Pb^+2^ stabilizes DNA G-quadruplexes1 we have focused attention on
the interaction of Pb^+2^ with the lipophilic nucleoside
5\'-t-butyl-dimethylsilyl-2\',3\',-di-O-isopropylidene guanosine 1.

We recently described a crystal structure of a K^+^ G-quadruplex formed
by stacking (G 1)8-K^+^ octamers.4 Now, we provide ^1^H and ^207^Pb
solution NMR and X-ray crystallographic evidence that Pb^+2^ also
templates formation of a particularly stable G-quadruplex. Comparison of
the K^+^ and Pb^+2^ crystal structures show that the divalent cation
leads to a more compact coordination cavity resulting in shorter
hydrogen-bonds in the Pb^+2^ G-quartet. These shorter hydrogen bonds
observed in the solid-state correlate well with solution ^1^H NMR data
that shows stronger hydrogen bonding for the Pb^+2^ G-quadruplex.
Competitive extraction experiments also show that G 1 prefers to
coordinate Pb^+2^ over K^+^ by at least 100:1. This study\'s conclusion
is that Pb^+2^ bound

G-quartets are thermodynamically more stable than the K^+^ G-quartets.

References:

1\. Smirnov, I.; Shafer, R. H. J. Mol. Biol., 2000, 296, 1-5.

2\. Brown, R. S.; Higerty, B. E.; Dewan, J. C.; Klug, A. Nature, 1983,
303, 543-546.

3\. Wedekind; J. E.; McKay, D. B. Nat. Struct. Biol. 1999, 6, 261-268.

4\. Forman, S. F.;Fettinger, J. C.; Pieraccini, S.; Gottarelli,G.;

**38. Structural biology of the GMTCXXC consensus sequence in the first
metal**

binding domain from the protein involved in Menkes disease, MerP, and
synthetic peptides

> T.M. DeSilva, G. Veglia, F. Porcelli, A. Prantner, and S.J.Opella.
> Department of Chemistry, University of Pennsylvania, Philadelphia PA
> 19104

There are single-site mutations that perturb the critical transport of
copper in humans resulting in Menkes and Wilson\'s diseases. Both genes
encode 1500 residue proteins with six repeats of a heavy metal binding
domain at the N terminus of the P-type ATPase. The metal binding domains
have homologous sequences containing the GMTCXXC motif also found in
many proteins involved in detoxification systems found in yeast and
bacteria. This sequence is able to bind and transport a host of
different heavy metals in various environments. The gene for the first
heavy metal binding motif (GMTCNSC) of the Menkes disease protein (MNK1;
residues 1-79) was synthesized, cloned, and expressed for biochemical
and structural studies. MNK1 binds various metals besides copper, such
as Hg(II) and Ag(I) which prefer a linear bicoordinate geometry, as well
as Cd(II) and Ni(II) which tend to bind proteins in an octahedral
fashion. EPR studies show MNK1 also binds Cu(II) which prefers a
tetrahedral or square planar orientation unlike Cu(I). This is
surprising since the two cysteine groups in GMTCXXC were shown to bind
Cu(I) in a linear bicoordinate manner and all the proteins containing
GMTCXXC studied thus far have linear bicoordinate metal centers. The
three-dimensional structure of the Cu(II) bound form of MNK1 was
determined and is the first structure in this family to be solved with a
metal center other than linear bicoordinate. Since the structure of MNK1
is very similar to MerP (mercury binding bacterial protein) variants of
MNK1 containing the MerP consensus motif, GMTCAAC, show how a change in
protein scaffolding affects metal binding. Three 18-residue peptides
corresponding to the metal binding loop of MerP show how a change in
register of the cysteines CAAC, CACA, and CCAA can fine tune mercury
metal selectivity. Understanding metal specificity using small molecules
may provide insight into new methods for heavy metal detoxification in
humans.

**39. Wilson\'s Disease Protein: The Ligand-binding Properties and
Copper-**

> **Dependent Domain-Domain Interactions**
>
> Svetlana Lutsenko^1^, Nininan Blackburn^2^, Mathew J. Cooper^1^, Brian
> C. MacArthur^1^, Martina Ralle^2^, Ruslan Tsivkovskii1. ^1^Department
> of Biochemistry and Molecular Biology , Oregon Health Sciences
> University, and ^2^Oregon Graduate Institute, Portland OR, 97201

Wilson\'s disease, an autosomal disorder associated with vast
accumulation of copper in tissues, is caused by mutations in a gene
encoding a copper-transporting ATPase (Wilson\'s disease protein, WNDP).
To elucidate the biochemical properties and molecular mechanism of WNDP,
we expressed, purified, and characterized the major functional domains
of WNDP: the N-terminal copper-binding domain and ATP-binding domain.
The independently folded N-terminal domain, containing six sequence
repeats, was shown to bind one copper per repeat, or 5.5-6 copper per
domain. Copper is bound in the reduced Cu(I) form and is linearly
coordinated by two Cys residues in the conserved GMTCxxC motif. The
ATP-binding domain also folds independently and binds the fluorescent
ATP analogue trinitrophenyl-ATP with high affinity. ATP competes with
trinitrophenyl-ATP for the binding site with the apparent affinity of
about 200 mM. We further demonstrate that the N-terminal copper-binding
domain of WNDP (N-WNDP) and the ATP-binding domain are involved in
specific protein-protein interactions. Strikingly, copper binding to
N-WNDP diminishes these interactions, suggesting that the
copper-dependent change in domain-domain contact may represent the
mechanism of the WNDP regulation. In agreement with this hypothesis,
N-WNDP induces conformational changes in ATP-binding domain as evidenced
by the altered nucleotide-binding properties of ATP-BD in the presence
of N-WNDP. The implications of these results for the WNDP function are
discussed. The developed assays can be utilized for detailed analysis of
the Wilson\'s disease mutations.

**40. Characterization of the Mouse Homologue of a Bacterial Arsenite
Translocating**

**ATPase**

> Hiranmoy Bhattacharjee, Ye-Shih Ho and Barry P. Rosen. Department of
> Biochemistry and Molecular Biology, Wayne State University, School of
> Medicine, Detroit, MI 48201

Resistance to arsenicals and antimonials is widespread in both
prokaryotes and eukaryotes. Gram-negative and Gram-positive bacteria
encode arsenical resistance (ars) operons that are found in chromosomes
as well as on plasmids. An ATP dependent membrane export pump encoded by
the arsA and arsB genes confers resistance. ArsA is a 63-kDa ATPase that
is allosterically activated by either As(III) or Sb(III), and ArsB is a
45-kDa integral membrane protein that serves as the anion translocating
subunit. The ArsAB pump extrudes As(III) or Sb(III) from inside the cell
to outside, thereby reducing their concentration to sub-toxic levels.

Genes encoding potential arsA homologues have been reported in many
members of every kingdom. Eukaryotic homologues are nearly ubiquitous.
For example, homologues of the E. coli ArsA ATPase have been identified
in the plant A. thaliana, in the yeast S. cerevisiae and in the soil
nematode C. elegans. Recently a human homologue (hARSA) was suggested to
be involved in the resistance to arsenite and cis-platin. While the
biological roles of these putative ArsAs are still unknown, such a
widespread protein is likely to have a nontrivial physiological
function.

We have recently isolated a mouse cDNA encoding a homologue of the
bacterial arsA gene and have determined the complete map of the genomic
mARSA DNA. The putative mouse ArsA (mArsA) polypeptide has 348 amino
acid residues that exhibit 98% identity with the human homologue and
about 29% identity and 49% similarity with either the A1 or A2 domains
of the E. coli R773 plasmid encoded ArsA protein. We have expressed the
recombinant mouse protein in E. coli by inserting the full-length cDNA
into the expression vector pET-28b and the purified protein has ATPase
activity. Further characterization of the enzyme is in progress. In an
effort to understand the physiological role of the protein, we have
constructed a targeted disruption of the mARSA gene in mouse embryonic
stem cells using a positive-negative selection strategy. Further
experiments are in progress to create a homozygous knockout mouse.

Supported by United States Public Health Service Grant GM55425

**41. Structure of the ArsA ATPase: the Catalytic Subunit of a Heavy
Metal**

Resistance Pump.

> Tongqing Zhou, Sergei Radaev, Barry P. Rosen and Domenico L. Gatti.
> Department of Biochemistry and Molecular Biology, Wayne State
> University School of Medicine, Michigan 48201, USA.

Active extrusion is a common mechanism underlying detoxification of
heavy metals, drugs and antibiotics in bacteria, protozoa, and mammals.
In Escherichia coli high-level resistance to arsenite and antimonite is
conferred by the ars operon of plasmid R773. The arsA and arsB genes of
the operon encode, respectively, the catalytic subunit (ATPase) and the
membrane subunit of a pump that extrudes arsenite and antimonite ions
from the cytosol. When expressed in the absence of ArsB, ArsA can be
isolated as a soluble ATPase that displays a 15-20 fold enhancement of
activity upon binding Sb(III). ArsA is composed of two homologous
domains (\>20% identity) connected by a linker of 23 amino acids. Each
domain contains a consensus sequence for a nucleotide binding site
(NBS), and both NBS are required for ATPase activity and antimonite
transport.

ArsA has been crystallized and the structure was determined by the
multiwavelength anomalous diffraction (MAD) of a selenomethionine
derivative and refined at 2.3 Å to an R-factor (R~free~) of 20.7 (26.2).
The structure reveals that arsenite and antimonite metalloids stimulate
ATPase activity by binding in a cluster that links the two homologous
domains of the enzyme. Two nucleotide binding sites (NBS), located at
the interface between domains, are in direct communication with the
metal cluster via a short stretch of residues. The relative positions of
the two NBS and the inferred mechanism of allosteric activation of ArsA
provide a useful model for the interaction of the catalytic domains of
ABC transporters such as CFTR and the P-glycoprotein. This work was
supported by U.S. Public Health Service grants GM55425 and AI43918.

**42. Application Of cDNA Microarray To The Study Of Arsenic Toxicology
And**

> **Carcinogenesis**
>
> Jie Liu^1^, Hua Chen^1^, Tong Lu^1^, Judy L. Mumford^2^, and Michael
> P. Waalkes^1.\ 1^Laboratory of Comparative Carcinogenesis, NCI at
> NIEHS, Research Triangle Park, NC, ^2^Epidemiology and Biomarker
> Branch, US EPA, Research Triangle Park, NC, USA

Arsenic (As) is a common environmental toxicant and known human
carcinogen. Epidemiological studies link As exposure to various diseases
and cancers. However, the molecular mechanisms for As toxicity and
carcinogenicity are not completely known. The cDNA microarray, a
high-throughput analysis of gene expression, was used to profile the
genetic events associated with inorganic As exposure. In murine liver
epithelial cells chronically exposed to As^+3^, the upregulation of many
oncogenes (such as c-myc, c-K-ras, c-met, erbB2, and Rb), and the
downregulation of certain growth factors such as IGF-II, were associated
with As-induced malignant transformation. In mice treated acutely with
As^+3^ and As^+5^, expression of many oxidative stress-related genes
(such as heme oxygenase 1) and of DNA damage-inducible genes (such as
gadd45) was markedly increased, while the expression of genes encoding
for drug metabolizing enzymes was suppressed. In liver biopsy samples
from As-exposed humans in Guizhou, China, expression of E2F, PCNA, HGF,
and superoxide dismutase was increased, while c-fos, rho6 protein, and
cytokeratin-18 and cytokeratin-8 were downregulated. In summary, the
microarray analysis revealed important aberrant gene expression patterns
occurring with As exposure in humans and rodents. These initial gene
array studies could be critical in future studies designed to more fully
elucidate the molecular mechanisms of As toxicity and carcinogenesis.

**Session 5. Metallotherapeutics and Disease**

**43. The Antiviral Activity of Titanyl (TiO^+2^) Sulfate Toward Human**

Cytomegalovirus

> ^1,2^Chad W. Schwietert, ^2^Nancy C. Gerber, ^1^John P. McCue,
> ^3^James J. McSharry. ^1^Gibson Institute for Medical Research, Santa
> Rosa, CA 95402; ^2^Department of Chemistry and Biochemistry, San
> Francisco State University, San Francisco, CA 94132; ^3^Center for
> Immunology and Microbial Diseases, Albany Medical College, Albany, New
> York 12208.

Human cytomegalovirus (HCMV) is an opportunistic pathogen that is
responsible for the life-threatening infections found in congenitally
infected infants, the immunocompromised, and immunosupressed transplant
patients. Retinitis, an infection caused by HCMV, is currently being
treated by ganciclovir, foscarnet, or cidofovir. However, these
antiviral drugs are not ideal due to their toxicity level and poor
bioavailability. In addition, the long-term usage of these antiviral
drugs has lead to a positive selection of viral mutants that are
resistant to these drugs. These various factors have initiated an active
search for antiviral agents for HCMV that are both low in toxicity and
highly bioavailable. Flow cytometry (FACS) drug susceptibility assay is
a novel method, which measures the percentage of cells expressing an
immediate early (IE) antigen to HCMV by using FITC labeled monoclonal
antibodies. This technique has permitted the testing of new antiviral
agents with different modes of action seen in current drugs. Using the
FACS assay and microscope examination, titanyl sulfate has been shown to
be affective in inhibiting viral replication. The IC50 for titanyl
sulfate against the laboratory strain AD169 of HCMV was determined to be
1 mM.

**44. Tachpyridine, A Novel Iron Chelator And A Potential Anti-Cancer
Agent In**

> **The Treatment Of Tumors With Mutated p53**
>
> R.D. Abeysinghe, B. Greene, M.C. Willingham, R.P. Planalp^2^, M.W.
> Brechbiel^3^, F.M. Torti, S.V. Torti. Wake Forest Univ. School of
> Medicine, Winston-Salem, NC; Univ. of New Hampshire, Durham, NH^2^;
> Radiation Oncology Branch, NIH^3^.

Iron is involved in numerous essential biochemical reactions ranging
from respiration to DNA synthesis. Consequently, iron deprivation has
been proposed as a strategy for inhibition of tumor cell growth.
Recently we described a novel iron chelator
N,N\'N\'-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane
(tachpyr) (Torti S.V. et al., 1998, Blood, 92, 1384). Tachpyr not only
inhibits growth of cultured tumor cells, but is actively cytotoxic. Here
we explore mechanisms underlying tachpyr cytotoxicity. Using several
criteria, including time-lapse video microscopy, DNA staining and TUNEL
assays, tachpyr was shown to induce apoptotic cell death. Since numerous
cytotoxic chemotherapeutic drugs induce apoptosis by activating
p53-dependent pathways, the requirement for p53 in tachpyr-mediated cell
death was assessed. Immunoblotting revealed rapid and robust activation
of p53 in tachpyr-treated cells. However, neither growth inhibition nor
cytotoxicity of tachpyr required p53. Thus, in 55 human cancer cell
lines the mean GI50 of tachpyr in cells with mutant p53 was virtually
identical to the GI50 in cells with wild type p53. In addition, H1299
cells expressing ecdysone-inducible p53 exhibited equivalent sensitivity
to tachpyr in the presence and absence of p53. Further, time-lapse video
microscopy and TUNEL assays demonstrated that both p53-null and
p53-wildtype cells underwent apoptotic cell death in response to
tachpyr. These results demonstrate that tachpyr initiates an apoptotic
mode of cell death that does not require functional p53. Since over 50%
of human tumors contain functionally defective p53, the ability of
tachpyr to induce apoptosis independently of p53 may offer an advantage
in antitumor therapy..

**45. Anti-inflammatory Properties of M40403, a Low Molecular Weight
Synthetic**

Superoxide Dismutase Mime

> D. Salvemini. MetaPhore Pharmaceuticals, 1910 Innerbelt Business
> Center Dr, St Louis, MO 63114, USA.

Under normal circumstances, formation of superoxide anion (O~2~^-^) is
kept under tight control by endogenous superoxide dismutase (SOD)
enzymes. However in acute and chronic inflammation, the production of
O~2~^-^ is increased at a rate that overwhelms the capacity of
endogenous SOD enzyme defence system to remove them. The results of such
imbalance results in O~2~^-^ mediated damage. We have developed a series
of low molecular weight synthetic mimetic (\'synzymes\') of the native
SOD enzyme (SODm). M40403 is a prototypic SODm possessing catalytic SOD
activity approaching that of the native MnSOD enzyme while at the same
time possessing outstanding chemical and biological stability. Unlike
other so-called SOD mimetics, M40403 selectively removes superoxide
without interfering with other relevant biological oxidants, such as
nitric oxide, peroxynitrite, or hydrogen peroxide. This important
property will allow us to develop a better understanding of the role of
superoxide in health and disease by selectively removing superoxide in
vivo. The pharmacological profile of M40403 in models of acute and
chronic inflammation as well as reperfusion injury will be presented.
The outcome of these studies support the clinical application of this
class of SODm in a variety of diseases driven by superoxide or the
product of its interaction with nitric oxide, peroxynitrite.

**46. Salen Mn Complexes, Combined SOD/Catalase Mimics with Broad**

Pharmacological Efficacy, are Protective in Models for Neurodegeneration

> Susan R. Doctrow. Eukarion, Inc., Bedford, Massachusetts, USA, 01731.

Salen Mn complexes are low molecular weight synthetic molecules that
catalytically inactivate two reactive oxygen species (ROS), superoxide
and hydrogen peroxide, hence mimicking the antioxidant functions of both
superoxide dismutase (SOD) and catalase. We believe that the ability of
these compounds to neutralize two ROS species and, in particular, toxic,
long-lived hydrogen peroxide, should be therapeutically advantageous.
For example, a prototype salen Mn complex, EUK-8, is protective in
cellular models in which CuZnSOD, which itself generates hydrogen
peroxide, is deleterious. Structural analogs of EUK-8 have been
developed that do not differ with respect to their SOD activities, but
that do exhibit increased catalase and cytoprotective activities in
vitro. One of these compounds, EUK-134, was more effective than EUK-8 in
certain in vivo models, including rodent models for stroke and
myocardial infarction. Salen Mn complexes are protective in a variety of
in vivo models for diseases in which oxidative stress has been
implicated, including models for inflammatory, cardiovascular, acute
respiratory, autoimmune, and neurological diseases. Many of these
studies have been published (see references). This presentation will
focus instead on more recent data further supporting the potential
usefulness of these compounds in treating neurodegenerative diseases.
One study was conducted in mice lacking the mitochondrial enzyme MnSOD
(sod2 -/- mice). These mice die within \~8 days (mean) of a
cardiomyopathy (Li et al., Nature Genetics 11:376, 1995) or, if treated
with MnTBAP, a synthetic SOD mimic that does not cross the blood-brain
barrier, die within \~14 days, rescued of the cardiomyopathy, but going
on to develop a fatal neurological disorder characterized by a profound
movement impairment and widepread spongiform brain pathology (Melov et
al., Nature Genetics 18:159, 1998). Treatment of sod 2-/- mice with
EUK-8 or EUK-134 increased their lifespan to \>20 days and, importantly,
rescued the pathological and other manifestations of the neurological
disorder. Furthermore, the treated mice exhibited higher brain levels of
cis-aconitase, an oxidation-sensitive mitochondrial enzyme whose
activity is decreased in the sod -/- mice. This demonstrates that the
compounds can protect the brain mitochondria from the highly localized
oxidative stress that occurs in the sod 2-/-mice. This is an observation
especially relevant to neurodegeneration, since mitochondrial
dysfunction is implicated in, for example, Alzheimer\'s and Parkinson\'s
diseases. A second study utilized a transgenic mouse model for familial
Amyotrophic lateral sclerosis (FALS) which develops muscle weakness
progressing to motorneuron degeneration, paralysis and death (e.g. Kong
and Xu, J. Neuroscience 18:3241, 1998). Chronic treatment with EUK-8 and
EUK-134 prolonged survival of FALS mice. In addition, treated mice
exhibited less oxidative damage to the spinal cord, as indicated by
protein carbonyl and malonyldialdehyde determinations. Overall, their
broad pharmacological efficacy suggests that SOD/catalase mimics such as
the salen manganese complexes may have therapeutic value in a wide
variety of ROS-dependent diseases. As these new findings indicate,
potential target diseases include severe neurodegenerative disorders
whose current treatments are unsatisfactory.

Selected references: efficacy of salen manganese complexes in disease
models:

Gonzalez, P.K., Zhuang, J., Doctrow, S.R., Malfroy, B., Benson, P.F.,
Menconi, M.J., and Fink, M.P. EUK-8, a synthetic superoxide dismutase
and catalase mimetic, ameliorates acute lung injury in endotoxemic
swine. 1995. Journal of Pharmacology and Experimental Therapeutics 275:
798-806

Pucheu, S., Boucher, F., Malfroy, B., and DeLeiris, J. Protective effect
of the superoxide scavenger EUK-8 against ultrastructural alterations
induced by ischemia and reperfusion in isolated rat hearts. 1995.
Nutrition (Suppl.) 11:582-584

Bruce, A.J., Malfroy, B., and Baudry, M. Beta amyloid toxicity in
organotypic hippocampal cultures: protection by EUK-8, a synthetic
catalytic free radical scavenger. 1996. Proc. Natl. Acad. Sci. (USA)
93:2312-2316.

Doctrow, S.R., Huffman, K., Marcus, C.B., Musleh, W., Bruce, A., Baudry,
M., and Malfroy, B. \"Salen manganese complexes: combined superoxide
dismutase/catalase mimics with broad pharmacological efficacy\" in
Antioxidants in Disease Mechanisms and Therapeutic Strategies. (H. Sies,
ed.). 1996. Advances in Pharmacology 38: 247-269.

Gianello, P., Saliez, A., Bufkens, X., Pettinger, R., Misseleyn, D.,
Hori, S., and Malfroy, B. EUK-134, a synthetic superoxide dismutase and
catalase mimetic, protects rat kidneys from ischemia-reperfusion-induced
damage. 1996. Transplantation 62:1664-1666.

Malfroy, B., Doctrow, S.R., Orr, P.L., Tocco, G., Fedoseyeva, E.V., and
Benichou, G. Prevention and suppression of autoimmune encephalomyelitis
by EUK-8, a synthetic catalytic scavenger of oxygen reactive
metabolites. 1997. Cellular Immunology 177:62-68.

Baker, K., Bucay Marcus, C., Huffman, K., Kruk, H., Malfroy, B., and
Doctrow, S.R. Synthetic combined superoxide dismutase/catalase mimics
are protective as a delayed treatment in a rat stroke model: a key role
for reactive oxygen species in ischemic brain injury. 1998. Journal of
Pharmacology and Experimental Therapeutics 284:215-221.

Rong, Y., Doctrow, S.R., Tocco, G., and Baudry, M. EUK-134, a synthetic
superoxide dismutase and catalase mimetic, prevents oxidative stress and
attenuates kainate-induced neuropathology. 1999. Proc. Natl. Acad. Sci.
(USA) 96:9897-9902.

**47. Peroxynitrite Decomposition Catalyzed by Water-Soluble Iron
Porphyrins**

> John T. Groves\* and Roman Shimanovich. Department of Chemistry,
> Princeton University, Princeton, New Jersey, USA, 08544.

Peroxynitrite, ONOO-, is a known cytotoxic agent, involved in a diverse
array of pathological conditions. Various peroxynitrite decomposition
catalysts and pathways are being explored to develop efficient
therapeutic agents that can safely remove peroxynitrite from cells and
tissues. Water-soluble iron porphyrins, such as FeTMPS and FeTMPyP, have
been shown to catalytically decompose peroxynitrite and to reduce
inflammation in vivo. Their reactions with peroxynitrite have been
explored in detail and plausible mechanisms that account for
experimental observations have been proposed. The reaction mechanisms by
which these two porphyrins react with peroxynitrite are very different.
This mechanistic difference derives from a key difference in the
reactivity of the highly oxidized porphyrin intermediates that are
produced during catalytic decomposition of peroxynitrite. Both, FeTMPS
and FeTMPyP, react fast and efficiently with peroxynitrite to yield
oxoFe(IV) compounds and nitrogen dioxide as the fist step in catalysis
(5x107M-1s-1 for FeTMPyP and 1x105M-1s-1 for FeTMPS). However, our
studies have shown that the oxoFe(IV) compounds of the two porphyrins
react differently with nitrogen dioxide and peroxynitrite that are
present. oxoFe(IV)TMPyP appears not to react with nitrogen dioxide or
nitrite, instead it reacts with peroxynitrite in a concerted manner to
isomerize it to nitrate. On the other hand, oxoFe(IV)TMPS reacts rapidly
with nitrogen dioxide (1x10^7^ M^-1^s^-1^) and nitrite (1.4x10^4^
M^-1^s^-1^) to yield the reduced Fe(III)TMPS. oxoFe(IV)TMPS also appears
to have some peroxynitrite isomerase activity, analogous to FeTMPyP.
Both mechanisms account for raid conversion of peroxynitrite to
primarily nitrate by FeTMPyP and FeTMPS. The FeTMPyP-catalyzed pathway
functions faster then the FeTMPS pathway. However, these mechanisms do
not explain the in vivo data that suggests that FeTMPS is a more potent
therapeutic agent then FeTMPyP.

**48. Development of Materials for Storage, Release, and Detection of
Nitric Oxide**

> A. S. Borovik, Department of Chemistry, University of Kansas,
> Lawrence, Kansas, USA, 66045.

Nitric oxide (NO) has been implicated to have an important role in
numerous biological functions. Various methods have been reported to
delivery NO in vivo and in vitro. However, there are few examples of
systems that reversibly bind NO. We have developed a new polymeric
material that is capable to reversibly bind NO. The polymer contains
discrete metal sites with a high affinity for NO. It is composed of
isolated four-coordinate Co(II) complexes immobilized in a highly
crosslinked and porous methacrylate host. An important consequence of
the NO binding event is a rapid and vivid color change of the material
from orange to dark brown-green. This dramatic color change leads to
immediate confirmation of the presence of nitric oxide in both the gas
and solution phases. Moreover, the immobilized Co(II) sites have a
significantly greater affinity for NO over other gaseous compounds such
as O2 and CO. The NO-loaded material releases NO under biologically
relevant conditions to cause the vascular relaxation (rabbit artery
assay). At the submicrogram level of material, \> 80% change in the
tension of a rabbit artery is observed. This NO-releasing material also
inhibits platelet formation. Small modifications of this material
produces a NO scavenging materials that can remove NO from a rabbit
artery milieu, which causes a constriction in the artery.

**49. Chemistry and Insulin Like Properties of Cobalt
2,6-pyridinedicarboxylate**

> **Complexes.**
>
> Luqin Yang,^1^ Debbie C. Crans, ^1^\* Susie M. Miller, ^1^ Agnete la
> Cour, ^1^ Oren P. Anderson^1^ and Gail R. Willsky. ^2^ ^1^Department
> of Chemistry Colorado State University, Fort Collins, Colorado, USA,
> 80523-1872, ^2^Department of Chemistry and Clinical Sciences, SUNY at
> Buffalo, Buffalo, New York, USA, 14214.

The synthesis and characterization of Co(II) and Co(III)
2,6-pyridinedicatboxylate (dipic^2-^) complexes are reported. Solid
state and X-ray characterization were performed of
\[Co(Hdipic)~2~\]•3H~2~O and \[Co(dipic)~2~Co(H~2~O)~5~\]•2H~2~O. Novel
coordination modes in these complexes are observed and will be
described. Solution studies including paramagnetic NMR and UV-vis
spectroscopy are done showing the high stability and low lability of the
Co(III) complex, whereas the Co(II) complexes show ligand exchange in
the presence of excess ligand. The chemical properties of these
compounds are compared to those of the VO~2~dipic^-^ complex. In
addition, the glucose lowering effects of these compounds in rats with
streptozotocin-induced diabetes were determined and compared to those of
VO~2~dipic^-^ and the vanadium compounds currently used in human studies
with diabetic patients.

**50. What Is the Active Vanadium Pool in NIDDM Patients Dosed With
Vanadyl**

> **(IV) Sulfate?**
>
> G. Willsky (1), P. Kostyniak (1), K. Halvorsen (2), and A. Goldfine
> (3). SUNY at Buffalo Sch. of Med. and Biomed. Sci., Buffalo, NY 14214
> (1), Smith College, Northhampton, MA (2) and Joslin Diabetes Center,
> Boston, MA, 02215 (3).

Vanadium (V),(25, 50, 100 mg elemental, daily) was given orally to 16
NIDDM patients for 6 weeks. The clinical portion of this work has been
published: Goldfine et al., (2000), Metabolism 49: pp400-410. Elemental
V was determined using GFAAS against known concentrations of V in a
serum, blood or urine matrix. Peak serum V levels were 16.0±5.1, 83.6±44
and 284.5±146 ng/ml respectively. Although large inter-individual
variability was found, peak serum V linearly correlated to dose
administered (R2 = 0.983). V loss from serum was fit to a
one-compartment model: t~1/2~ values were 7.7 days ± 3.2 for the 50 mg V
dose) and 5.3±1.4 days for the 100 mgV dose, (statistically different
with P \< 0.05). At steady state, urine V clearance was 0.26±0.25 and
0.95 ± 0.82 mg in the 50 and 100 mg V groups respectively, consistent
with absorption of 1 percent or less of the administered dose. A higher
frequency of patients responded to V, as determined by euglycemic clamp,
in the 2 higher dose groups (3/5 and 4/8 respectively) compared to the
lowest dose group( 0/3). Peak V in whole blood and serum V
concentrations showed a linear correlation with (R2= 0.95). However,
Area Under the Curve analysis of the Serum V and Blood V with time for
the patients receiving 100 mg V showed that there was 1.7 ± 0.45 more
vanadium in the serum compared to the blood.

There was no significant correlation of any of the clinical responses
(euglycemic clamp at 2 insulin values) to ln peak serum. Preliminary
data using stepwise multiple regression analysis with all patients was
done with the clinical responses (euglycemic clamp at high and low
insulin concentrations, and lowering of fasting blood glucose) and ln
peak serum V as explained variables and the following as predictor
variables: Blood levels of triglyceride, HDL, VLDL, Glycohemoglobin,
serum albumin, globuin, and total protein; Body Mass Index, hematocrit,
and gravimetric lipid in serum. Glycohemoglobin was a negative predictor
of ln peak serum V ( P=0.009, R2 = 0.38) and glycohemoglobin was a
positive predictor of the euglycemic clamp at high insulin values (P=
0.01, R2=0.39). There were no statistically significant predictors for
the euglycemic clamp response at low insulin concentration or the
lowering of fasting blood glucose levels.

These studies show that vanadyl sulfate improved insulin sensitivity and
fasting blood glucose levels in some, but not all NIDDM patients, that
vanadium did not distribute the same in serum and erythrocytes and that
although Vanadium accumulation into serum shows the expected dose
response relationship Vanadium pools other than total serum Vanadium are
related to its insulin-like effect in this patient population.

**51. Vanadium and Insulinomimesis: A Possible Role of
Phosphatidylinositol 3-**

Kinase (PI3-K)

> Ashok K. Srivastava, Jean-François Théberge, Michel Bernier, and
> Sanjay K. Pandey. Research Centre, Centre hospitalier de l\'Université
> de Montréal (CHUM) and Department of Medicine, University of Montreal,
> Montreal (Quebec) H2W 1T8 Canada.

The salts of trace metal vanadium have been shown to mimic many effects
of insulin including the anti-diabetic effects in animal models of
diabetic mellitus as well as in some human subjects. In an attempt to
explore the molecular mechanism of insulin-mimesis by vanadium salts, we
have investigated the effect of vanadyl sulphate (VS) on key components
of insulin signalling pathway in Chinese hamster ovary (CHO) cells
overexpressing insulin receptor (IR). Treatment of IR overexpressing
cells with VS resulted in an enhanced tyrosine phosphorylation of
mitogen-activated protein kinases (MAPK), ERK 1 and ERK 2 along with the
activation of MAPK kinase (MEK) and c-raf activities, and ras
activation. Pre-incubation with wortmannin and LY294002, two
structurally and mechanistically distinct inhibitors of PI3-K blocked
VS-induced activation of ERK 1/ERK 2, MEK, c-raf as well as ras. VS also
stimulated PI3-K activity and glycogen synthesis which were completely
attenuated by pre-treatment with wortmannin and LY294002. Interestingly,
VS-induced responses were not associated with an increase in the
tyrosine phosphorylation of IR. In summary, these results demonstrate
that VS stimulates the PI3-K and Ras/ERK 1/ERK 2, PI3-K signalling
pathway, independent of IR tyrosine phosphorylation. It is suggested
that VS-induced activation of this pathway plays a key role in mediating
the insulinomimetic effects of vanadium salts.

**Other Topics**

**52. NIH Support for Bioinorganic Chemistry**

> Peter C. Preusch. National Institute of General Medical Sciences, NIH,
> Bethesda, Maryland, USA, 20892.

This poster will present data on the distribution of NIH support for
various areas of bioinorganic chemistry and metallobiochemistry
research. It will include information on the study sections which review
work in this area as well as the NIH component institutes funding the
work.

**53. In the Beginning... The Evolutionary Origin of Aerobic
Metabolism**

G.C. Dismukes^1^, S.V. Baranov^2^, G.M. Ananyev^1^, V.V. Klimov^2^, R.
Watt^1^, A. Tyryshkin^1^ ^1^.Princeton University, Department of
Chemistry & Princeton Environmental Institute, Princeton NJ; ^2^.Russian
Acad. Sci., Inst Basic Biological Problems, Pushchino, Russia.

The development of aerobic metabolism was one of the most important
breakthroughs in evolution. It generates 18 times more energy (ATP) per
metabolic input (glucose) than anaerobic metabolism. This transition was
spurred by another major breakthrough in metabolic evolution: the use of
water as a reductant for photosynthesis. The earth's O~2~ rich
atmosphere and all oxygenic life on earth arose after the appearance of
the first O~2~-producing photosynthetic cyanobacteria circa 3 billion
years ago. Evolutionary biologists have been unable to explain how the
first primitive bacteria acquired the ability to use water as a
four-electron donor in place of the more easily oxidized one- and
two-electron carbon and sulfur compounds utilized by their evolutionary
precursors. Analysis of all oxygenic photosynthetic organisms studied to
date reveals that they all use the same metallo-enzyme to catalyze this
reaction. The photosystem II-water-oxidizing complex (PSII-WOC) is
powered by an invariant inorganic core, containing Mn~4~O~x~Ca~1~Cl~y~.
How did this complex core assemble in the first cyanobacterium and why
have no alternative core types evolved in contemporary organisms? A clue
to the first question is suggested by the enormously higher atmospheric
CO~2~ concentration that existed in the archaean period (102-104 x
current level), resulting in greatly elevated concentration of
bicarbonate in seawater. At the predicted bicarbonate concentration the
speciation of Mn^2+^ (and Ca^2+^) in solution would have been altered by
chelation, hydrolysis and oxidation to yield Mn~X~(HCO~3~)~y~(OH)~Z~
clusters in solution. These complexes are more easily oxidized than
aquo-Mn^2+^ and undergo multi-electron oxidation reactions. We have
presented evidence showing that in contemporary photosynthetic organisms
even low levels of bicarbonate ion accelerate the rate of assembly of
the inorganic core of the PSII-WOC starting from the free inorganic
cofactors and the apo-enzyme in solution.(1) We have identified two
sites, involving Mn^2+^ and Ca2+ affinities, where bicarbonate
stimulates the formation of a functional inorganic core in the apo-WOC.
A direct role for bicarbonate in biogenesis of the holo-enzyme is thus
indicated. We hypothesize that Mn~X~(HCO~3~)~y~(OH)~Z~ clusters would
have been abundant building blocks in the archaen seas from which to
nucleate assembly of a functional inorganic core within the
photosynthetic bacterial precursor that evolved, by spontaneous
mutations, to become the first stable O~2~-evolving cyanobacteria.
Additional evidence for this hypothesis comes from synthetic work
showing that simple phosphinate anions (RRPO~2~^-^), which function like
non-hydrolyzable iso-valent \'bicarbonate surrogates\', induce
spontaneous assembly of tetra-manganese-oxo clusters,
Mn~4~O~4~(O~2~PPh~2~)~6~, having a cubane core structure analogous to
the WOC core.(2) Significantly, the cubanes are functional mimics of the
overall in vivo process of water oxidation/O~2~-evolution:
Mn~4~O~2~(O~2~PPh~2~)~6~ + 2 H~2~O ⇒ Mn~4~O~4~(O~2~PPh~2~)~6~ Æ
Mn~4~O~2~(O~2~PPh~2~)^5+^ + O~2~PPh^2-^ + O~2~

1\. Baranov, S. V. et al. Biochemistry 2000. 39: in press.

2\. Ruettinger, W. et al.Inorganic Chemistry, 1999. 38: 1036; 2000. 39,
1021; JACS, submitted.

ADDITIONAL

BIOSKETCHES

(IN ALPHABETICAL ORDER)

**Georgia M. Arvanitis, PhD, Professor, Chemistry, The College of New
Jersey.** Ph.D., Chemistry (1987) Princeton University. The College of
New Jersey is a four-year undergraduate institution. My interests
include providing opportunities for involving outstanding chemistry and
biology majors in research projects. The main project underway in my lab
is a study of platinum antitumor agent. The work involves the synthesis
of platinum imidazothiazole, imidazole and thiazole complexes and their
subsequent screening for cytotoxicity in leukemia cell lines. Structural
and synthetic publications have resulted from this work. I am currently
involved in determining the mechanism of action of this class of
potential drugs. The fact that this work is such an important scientific
problem really attracts students and gives me the chance to show them
how a long-term research project is carried out by a team of scientists.

Representative Publications:\
1. C.L. Baird, A.E. Griffitts, S. Baffic, P. Bryant, B. Wolf, J. Lutton,
M. Berardini and G.M. Arvanitis: Synthesis, Characterization and
Antitumor Activity of Platinum Triamine Complexes Containing
Imidazothiazole Ligands. Inorg. Chim. Acta, 256, 253-262 (1997).\
2. G.N. Parkinson, G.M. Arvanitis, L. Lessinger, S.L. Ginell, R. Jones,
B. Gaffney and H.M. Berman: The Crystal and Molecular Structure of a New
Z-DNA Crystal Form: d\[CGT(2-NH2)ACG\] and its Platinated Derivative.
Biochemistry, 34, 15487-15495 (1995).\
3. D. Gibson, H.M. Berman and G.M. Arvanitis: A Synthetic and Kinetic
Study of Model Complexes for Formation of Pt(II) Mediated DNA-Protein
Crosslinks. Inorg. Chim. Acta, 218, 11-19 (1994).\
4. G.M. Arvanitis, M.E. Berardini, T.B. Acton and P.E. Dumas: Synthesis
and Characterization of Tetraphenylantimony(V) derivatives of Mercapto-
and Selenopyridine-N-Oxide. Phosphorus and Sulfur, 182, 127-135 (1993).

**Bruce A. Averill, PhD, Professor, E. C. Slater Institute & University
of Amsterdam.** Ph.D. in Inorganic Chemistry, M.I.T., 1973.;
Postdoctoral Fellow in Biochemistry, Brandeis University, 1973-1974.;
Postdoctoral Fellow in Biochemistry, Univ. of Wisconsin, Madison,
1974-1976.; Asst., Assoc. Professor, Chemistry, Michigan State
University, 1976-1982.; Assoc. Prof., Professor, Chemistry, University
of Virginia, 1982-1994.; Professor of Biochemistry, E.C. Slater
Institute, University of Amsterdam, 1994-. Research in bioinorganic
chemistry: purple iron-containing phosphatases; dissimilatory nitrite
reductases; models for nitrogenase metal-sulfur clusters; synthetic
copper (I) complexes for olefin/alkane separation.\
Recent papers:

1\. M. Merkx and B. A. Averill, \"Probing the Role of the Trivalent
Metal in Phosphate Ester Hydrolysis: Preparation and Characterization of
Purple Acid Phosphatases Containing M(III)Zn(II) Active Sites (M(III) =
Al, Ga, In Fe), Including the First Example of an Active Aluminum
Enzyme\", J. Am. Chem. Soc., 121, 6683-6689 (1999).\
2. M. Merkx, M. W. H. Pinkse, and B. A. Averill, \"Evidence for
Non-Bridged Coordination of p-Nitrophenylphosphate to the Dinuclear
Fe(III)-M(II) Center in Bovine Spleen Purple Acid Phosphatase During
Enzymatic Turnover\", Biochemistry, 38, 9914-9925 (1999).\
3. M. W. H. Pinkse, M. Merkx, and B. A. Averill, \"Fluoride Inhibition
of Bovine Spleen Purple Acid Phosphatase: Characterization of a Ternary
Enzyme Phosphate Fluoride Complex as a Model for the Active Enzyme
Substrate Hydroxide Complex\", Biochemistry, 38, 9926-9936 (1999).\
4. B. A. Averill, Dissimilatory Nitrite and Nitric Oxide Reductases,
Chem. Rev., 96, 2951-2964 (1996).

**Ian Robert Baird, PhD, Research Scientist, Chemistry, AnorMED, Inc.**
Post-Doc (1999-present) Industrial Research Fellow, AnorMED, Inc.; Ph.D.
(1994-1999) University of British Columbia. Supervisors: Brian R. James
and Kirsten A. Skov. Thesis Title: Fluorinated Nitroimidazoles and their
Ruthenium Complexes: Potential Hypoxia-Imaging Agents. Research
Interests: (Past) Development of novel transition metal-based complexes
and 18F-radiolabelled imidazoles for the imaging of hypoxia in tumours.
(Current) The use of transition metal-based complexes as reversible
enzyme inhibitors.\
Publications:

1\. Ian R. Baird, Steven J. Rettig, Brian R. James, Kirsten A. Skov,
Synthesis and X-ray Structural Characterization of the Ruthenium
&#61538;-Diketonato Complexes: Ru(hfac)3, cis-Ru(hfac)2(MeCN)2 and
cis-Ru(hfac)(acac)(MeCN)2, Can. J. Chem. 77 (1999) 1821-1833.\
2. Alexander V. Kachur, Sydney M. Evans, Chyng-Yann Shiue, William R.
Dolbier, Jr., An-Rong Li, Alex Roche, Kirsten A. Skov, Ian R. Baird,
Brian R. James, Cameron J. Koch, Synthesis of New Hypoxia Markers EF1
and \[18F\]-EF1, Appl. Rad. Isot. 51 (1999) 643-650.\
3. Ian R. Baird, Steven J. Rettig, Brian R. James, Kirsten A. Skov,
Synthesis and Characterization of Homoleptic Ruthenium(II) Imidazole
Complexes, and a Carbonyl Species Derived by CO Abstraction from DMF,
Can. J. Chem. 76 (1998) 1379-1393.

**Girish C. Barua, PhD, MD, Technology Specialist, Office of Technology
Transfer, National Institutes of Health.** My responsibilities are to
commercialize NIH technologies to the private sector in the areas of
cancer therpeutics, infection disease and general medicine.

**Marjam G. Behar, PhD, Scientific Review Administrator, Center for
Scientific Review, National Institutes of Health.** Before joining NIH
in 1980, Dr.Behar served on the staff of department of anesthesiology of
University of Pennsylvania School of Medicine, studying cerebral blood
flow in the brain using krypton 85 tracers. Executive Secretary of the
Bioanalytical and Metallobiochemistry Study Section, 1980-1984. Special
Review Section, 1984-present, reviews of chemistry and biophysics.

**Barbara Anne Bench, Graduate Student, Chemistry Department, Brown
University.** I am a graduate student at Brown University. The focus of
my research has been the synthesis and reactivity of bionspired
catalysts, metal complexes and materials based upon three dimensional,
perfluorophthalocyanines. As part of my interest in medical application
we are currently testing the use of one of these complexes as an anti
cancer agent for photodynamic tumor therapy.

Recent Publications:\
1. Gorun, S.M., Bench, B.A., Beveridge,A.C., Calasso, I.G., Diebold,
G.J., van Lier, J .\"Synthesis, Structural Elucidation, and Biological
Activity of the First Perfluorinated Three-Dimensional
Metallo-Phthalocyanine\" In Preparation.\
2. Gorun, S.M., Bench, B.A., Carpenter, G., Beggs, M.W., Mague, J.T.,
Ensley, H.E., \"Synthesis and Structural Characterization of Non-Planar
Perfluoro Phthalonitriles\", J.Fluorine Chemistry, 1998, 91, 37.\
3. United States Patent 5,596,124 Methods for Safening Herbicides in
Cereal Crops Using 5-Aryloxy-1,2-(Disubstitued)Benzene Compounds, 1994.

**Mike Berardini, PhD, Adjunct Professor, Chemistry, The College of New
Jersey.** Ph.D., Chemistry, December 1996 from Rutgers University;
Currently adjunct professor at The College of New Jersey. Research
interests include bimetallic metallocene-platinum complexes as potential
chemotherapeutic agents. This includes the design of organic ligands to
couple Cp2TiCl2 and (DMSO)2PtCl2 moieties in order to synthesize
bimetallic complexes which contain two active anti-tumor fragments in a
prodrug form. More recent interests include the design, synthesis and
formulation of novel biocides for oral care applications.

Representative Publications:\
1. C.L.Baird, A.E. Griffitts, S. Baffic, P. Bryant, B. Wolf, J. Lutton,
M. Berardini and G.M. Arvanitis: Synthesis, Characterization and
Antitumor Activity of Platinum Triamine Complexes Containing
Imidazothiazole Ligands. Inorg. Chim. Acta, 256, 253-262 (1997).\
2. M. Berardini, T.J. Emge and J.G. Brennan: Heterobimetallic Pt-Ti
Complexes: Potential Anticancer Drugs. Inorg. Chem., 32, 2724-2728
(1993).\
3. G.M. Arvanitis, M.E. Berardini, D. Allardice, and P. E. Dumas:
Structure of 2-bis-Selenopyridine- N-oxide and its Formation from
Tetraphenylantimony(V)selenopyridine-N-oxide. J. Chem. Cryst., 24,
421-423 (1994).\
4. G.M. Arvanitis, M.E. Berardini, T.B. Acton and P.E. Dumas: Synthesis
and Characterization of Tetraphenylantimony(V) derivatives of Mercapto-
and Selenopyridine-N-Oxide. Phosphorus and Sulfur, 182, 127-135 (1993).

**Lawrence J. Berliner, PhD, Professor, Chemistry, Ohio State
University.** Metalloproteins: lactalbumin

**Andrew Cameron Beveridge, Graduate Student, Department of Chemistry,
Brown University.**

1\. DeFotis, G.C.; Beveridge, Andrew C.; Wilkens, M.J.; Fuller, Z.J.;
McMahon, J.G.; Wallo, C.D. &#8220;Insulating ternary magnetic
Co1-xMnyFex-yCl2&#61623;H2O.&#8221; J. Appl. Phys. (2000), 87(9),
6540-6542.\
2. Beveridge, Andrew C.; McGrath, Thomas E.; Diebold, Gerald J.;
Karabutov, Alexander A. &#8220;Photoacoustic shock generation in carbon
suspensions.&#8221; Appl. Phys. Lett. (1999), 75(26), 4204-4206.\
3. McGrath, Thomas E.; Beveridge, Andrew C.; Diebold, Gerald J.
&#8220;Laser-induced \"regeneration\" of colloidal particles: the
effects of thermal inertia on the chemical reactivity of laser-heated
particles.&#8221; Angew. Chem., Int. Ed. (1999), 38(22), 3353-3356.\
4.McGrath, Thomas E.; Beveridge, Andrew C.; Diebold, Gerald J.
&#8220;Sonoluminescence initiated by laser irradiation of carbon
suspensions.&#8221; Appl. Phys. Lett. (1998), 73(8), 1029-1031.

**Hiranmoy Bhattacharjee, PhD, Assistant Professor-Research,
Biochemistry and Molecular Biology, Wayne State University School of
Medicine.** Our objective is to understand arsenical resistance
mechanism(s) in mammals and their role in conferring cross-resistance to
metal containing anticancer drug, cisplatin. Towards this goal, we are
generating knockout mouse model to understand the function of putative
gene(s) that are thought to be involved in arsenical resistance. Another
area of active research is to understand the molecular enzymology of
arsenical resistance in bacteria.

Selected reviews: Biochim. Biophys. Acta, 1461:207-15 (1999); Adv. Exp.
Med. Biol. 456:159-81 (1998); Methods Enzymol. 292, 82-97 (1998).

**Michael K. Bowman, PhD, Staff Scientist, Macromolecular Structure &
Dynamics, Pacific Northwest National Laboratory.** Dr. Bowman has been
at Pacific Northwest National Laboratory for seven years and was
previously at Argonne National Laboratory for seventeen years. He has
helped pioneer the application of pulsed electron paramagnetic resonance
spectroscopy and 2 dimensional methods of ESEEM and HYSCORE to metal
ions and proteins including bacterial photosynthesis, 2Fe2S proteins,
metal inhibition of cyt b6f complex.

**Jorge Arturo Briones, Pre-IRTA, Metabolic Dieseases Branch, NIDDK.** I
am a Bachelor of science in Chemistry. I have worked in a Bioinorganic
laboratory, a medicinal chemistry laboratory, and am currently working
in a microbiology laboratory. I am interested in all interfaces between
medicine, chemistry, and biology.

**Pechimuthu J Britto, PhD, Research Fellow, Laboratory Of Biochemistry
And Genetics, NIDDK.**

I had been working on \"Electrocatalysis at Carbon Nanotubes\". I have
studied different electrochemical reactions at the carbon nanotube
electrodes to find out the catalytic properties of nanotube surface
compared to the other carbon electrodes. Currently I have been working
on the in vitro posttranslational modification of tubulin.

**Joan Broderick, PhD, Assistant Professor, Department of Chemistry,
Michigan State University.** Ph.D. Northwestern U. w/ Tom O\'Halloran;
Postdoc MIT with JoAnne Stubbe; Asst. Prof. Amherst College 1993-1998;
Asst. Prof. Michigan State U. 1998-present. Research Interests:
Iron-sulfur clusters in biological radical generation, biosynthesis of
iron-sulfur clusters

**Henry Bryant, PhD, Laboratory of Diagnostic Radiology Research,
National Institutes of Health.** Synthesis and evaluation of new MR
imaging agents.

**Jeff W.M. Bulte, PhD, Staff Scientist, Lab of Diagn Radiology
Research, National Inst of Health.** 1991, PhD -University of Groningen,
The Netherlands; 1992-present: NIH, Lab of Diagn Radiology Research,
Position: Title 42 Staff Scientist Research interest: Molecular and
Cellular Imaging, MR contrast agents, Biology of iron, Stem cells. See
PNAS 96, 15256-15261 (1999).

**John A. Bumpus, PhD, Professor of Chemistry, Chemistry, University of
Northern Iowa.** Dr. Bumpus is a Professor of Chemistry at the
University of Northern Iowa. His research interests focus on the
structure, function and mechanisms of action of heme containing enzymes.
Other research interests center on developing a better understanding of
the mechanisms by which fungi mediate bioremediation of contaminated
water and soil.

Selected Publications:

1\. Chang, H.C., R.D. Holland, J.A. Bumpus, M.I. Churchwell and D.R.
Doerge (1999) Inactivation of Coprinus cinereus peroxidase by
4-chloroaniline during turnover: comparison with horseradish peroxidase
and bovine lactoperoxidase. Chemico-Biological Interactions
123:197-217.\
2. Bumpus, J.A. (1998) Perspectives on the use of White Rot Fungi in
Bioremediation Technologies. In: Bioremediation:Principles and Practices
Volume II. (Eds. R.L. Irvine and S. K. Sikdar)Technomic Publishing Co.,
Inc., Lancaster, PA. pp. 67-109.\
3. Tatarko, M. and Bumpus, J.A. (1997) Further Studies on the
Inactivation by Sodium Azide of Lignin Peroxidase from Phanerochaete
chrysosporium. Arch. Biochem. Biophys. 338:200-209.\
4. Bumpus, J.A. (1995) Microbial Degradation of Azo Dyes. In:
Biotransformations:Microbial Degradation of Health-Risk Compounds. (Ed.
V.P. Singh) Elsevier, Amsterdam, pp. 157-176.\
5. Bumpus, J.A., Tatarko, M., Chang, C.-W. (1993) Inactivation of
Lactoperoxidase by 4-Chloroaniline. Journal of Agriculture and Food
Chemistry 41:2197-2201.

**Beth R. Cameron, PhD, Senior Scientist, Chemistry, AnorMED Inc..**
1997-present Senior Scientist-AnorMED Inc.; 1995-6 Post-doctoral
fellow-University of Windsor-supervisor-Prof. Steve Loeb; 1994
Post-doctoral fellow-University of Twente (Netherlands)-supervisor-Prof.
David Reinhoudt; 1993 PhD. University of Victoria-supervisor-Prof. Alex
McAuley. Research interests include supramolecular transition metal
chemistry, molecular recognition and bioinorganic chemistry. More
recently, the use of coordination chemistry in medical applications.

Most Recent Publications:\
1. \"Calixarene Metalloreceptors. Synthesis and Molecular Recognition
Properties of Upper-Rim Functionalized Calix\[4\]arenes Containing an
Organopalladium Binding Site.\" Beth R. Cameron, Stephen J. Loeb, Glenn
P. A. Yap Inorg. Chem., 1997, 36, 5498-5504.\
2. \"Bis(amido)calix\[4\]arenes in the pinched cone conformation as
tunable hydrogen bonding anion receptors.\" Beth R. Cameron and Stephen
J. Loeb Chem. Commun. 1997, 573.\
3. \"Calixarene metalloreceptors. Upper-rim functionalized
calix\[4\]arenes containing an organopalladium binding site.\" Beth R.
Cameron and Stephen J. Loeb Chem. Commun. 1996, 2003.\
4. \"Transition Metal Complexes as Both Host and Guest. Second-sphere
Coordination Between a Pt-Azacrown Ether Host and a Pt-NH3 Guest.\" Beth
R. Cameron, Sonia S. Corrent, Stephen J. Loeb Angew. Chem. Int. Ed.
Engl., 1995, 34, 2689\
5. \"Transition Metal Complexes of Lower Rim 1,3-Diphosphinite and
1,3-Diphosphino Calix\[4\]arenes.\" Beth R. Cameron, Frank C. J. M. van
Veggel, David N. Reinhoudt J. Org. Chem, 1995, 60, 2802.

**James W. Canary, PhD, Associate Professor, Chemistry, New York
University.**

Research Interests: Zinc enzyme inhibitors and models, dinuclear enzyme
mimics, stereodynamic chiral coordination complexes, application of
chiroptical methods to solution studies of zinc complexes, solution
speciation of spectroscopically silent metal complexes, chiral metal ion
sensors and switches, determination of absolute configuration and
enantiomeric excess by circular dichroism methods.\
Recent Publications:\
1. Zahn, S.; Canary, J.W. \"Electron-Induced Inversion of Helical
Chirality in Copper Complexes of N,N-Dialkylmethionines,\" Science,
2000, in press.\
2. Chiu, Y.-H.; dos Santos, O.; Canary, J.W. \"Conformational Control of
Propeller-Like Chirality in Zn(II) Complexes: Tightly Balanced Steric
Bias,\" Tetrahedron, 1999, 55, 12069.\
3. Zahn, S.; Canary, J.W. \"Absolute Configurations of Primary Amines
from Exciton-Coupled Circular Dichroism Spectra of Cu(II) Complexes of
their N,N-Bisquinaldyl Derivatives,\" Org. Lett., 1999, 1, 861-4.\
4. Xu, X.; Lajmi, A.R.; Canary, J.W. \"Acetaldehyde Hydration by
Zinc-Hydroxo Complexes: Coordination Number Expansion During
Catalysis,\" Chem. Commun., 1998, 24, 2701-2.\
5. Canary, J.W.; Allen, C.S.; Castagnetto, J.M.; Chiu, Y.-H.; Toscano,
P.J.; Wang, Y. \"Solid State and Solution Chracterization of Chiral,
Conformationally Mobile Tripodal Ligands,\" Inorg. Chem., 1998, 37,
6255-62.\
6. Castagnetto, J.M.; Canary, J.W. \"A Chiroptically Enhanced
Fluorescent Chemosensor,\" J. Chem. Soc., Chem. Commun., 1998, 203-4.\
7. Zahn, S.; Canary, J.W. \"Redox-Switched Exciton-Coupled Circular
Dichroism: A Novel Strategy for Binary Molecular Switching,\" Angew.
Chem., Int. Ed. Eng., 1998, 37, 305-7.

**Ty Caudle, PhD, Assistant Professor, Chemistry and Biochemistry,
Arizona State University.**

Ph.D., Duke University, 1993: kinetics related to iron transport
phenomena.; NIH Postdoctoral Fellow, University of Michigan, 1994-1997:
reactivity of manganese coordination compounds as models for
photosynthetic oxygen evolution processes. Assistant Professor, Arizona
State University, 1997-present: biomimetic carbon dioxide reactivity of
coordination complexes, models for biotin-dependent enxymes, magnesium
coordination chemistry.

**Winslow S. Caughey, PhD, Special Volunteer, Laboratory of Persistent
Viral Diseases, NIAID,NIH.**

Formerly, Professor of Biochemistry, Colorado State University. Research
interests: Hemeprotein biochemistry with an emphasis on reactions with
oxygen, carbon monoxide, and nitric oxide. Control of prion(TSE)diseases
with tetrapyrroles.

1\. \"Porphyrin and phthalocyanine antiscrapie compounds\", S.A.Priola,
A.Raines, W.S.Caughey, Science, 2000, 287, 1503-1506.

2\. \"Inhibition of protease-resistent prion protein formation by
porphyrins\", W.S.Caughey, etal., PNAS, 1998.

**Richard Chang, MD, Physician/ Interventional Radiologist, Radiology,
WG Magnusson Clinical Center/ NIH.** SCVIR., RSNA Interests:
Thrombolytic therapy. Development of active embolic agents using
microsphere technology.

**Madhuri Chattopadhyay, Graduate Student, Chemistry and Biochemistry,
University of Maryland, College Park.** I am a MS student at the chem
and biochem dept at Univ of Maryland, College park. I am working with
Prof Steven Rokita on nickel-induced oxidative modifications of
nucleosomes.

**Seema Choudhary, MD, Researcher, Chemistry, University at Buffalo.**
Research has been done in following areas: RNA Cleavage by using
Different metal ions. Schiff base metal Complexes. Computational Study
of VOC\'s. Environmental study of different metal ions in a river
systems.

**Michael J. Clarke, PhD, Professor, Chemistry, Boston College.** Metal
ion interactions with nucleic acids. Ruthenium-containing
pharmaceuticals. Biological effects of metallonitrosyl complexes.

1\. Frasca., D.R; Clarke, M.J., \"Alterations in the Binding of
\[Cl(NH3)5RuIII\]2+ to DNA by Glutathione: Reduction, Autoxidation,
Coordination, and Decomposition\", Journal of the American Chemical
Society 1999, 121, 8523-8532.\
2. Clarke, M. J., Zhu, F., Frasca, D., \"Non-Platinum Chemotherapeutic
Metallopharmaceuticals,\" Chemical Reviews 1999, 99, 2511-2533.\
3. Zhao, M.; Clarke, M. J., \"Trans-Pyridine Tetraammine Complexes of
RuII and RuIII with N7-Coordninated Purine Nucleosides\", Journal of
Biological Inorganic Chemistry 1999, 4, 318-324.\
4. Zhao, M.; Clarke, M. J., \"Effects of Trans-Pyridine Ligands on the
Binding and Reactivity of RuII and RuIII Ammine Complexes Coordinated to
Guaninek7 on DNA,\" Journal of Biological Inorganic Chemistry 1999, 4,
325-340.

**Seth M. Cohen, PhD, Postdoctoral Fellow, Chemistry, M.I.T.** N.I.H.
Postdoctoral Fellow Feb. 1998 - present. Advisor: Prof. S.J. Lippard;
Ph.D. Aug. 1994 - Dec. 1998. Advisor: Prof. K.N. Raymond; B.S. Aug.
1990 - June 1994. Advisor: Prof. R.M. Waymouth. Research interests
include studies in biological iron transport (JACS 1998, 120,
6277-6286), development of MRI contrast agents, and elucidating protein
interactions with cisplatin-modified DNA.

**James Cowan, PhD, Professor, Department of Chemistry, Ohio State
University.** Jimmy Cowan earned a B.Sc. in Chemistry from the
University of Glasgow in 1983, and a Ph.D. in Organic and Theoretical
Chemistry from the University of Cambridge in 1986. He was a NATO
postdoc with H. B. Gray at the California Institute of Technology. In
1988, he accepted a position in the Department of Chemistry at the Ohio
State University and was promoted to Full Professor in 1996. Research
interests are focused on understanding the reaction mechanisms of
oxido-reductase enzymes; the mechanism of assembly of complex metal
cofactors; the biological chemistry of the alkali and alkaline earth
ions, the design of inorganic drugs to target viral and regulatory RNA
motifs. These problems are tackled using a variety of physical, chemical
and biological techniques.

Recent publications include:

1\. \"Biological Iron-Sulfur Cluster Assembly. Detection of Kinetic
Intermediates by Time Resolved Fluorescence Spectroscopy.\" J. Am. Chem.
Soc. 120, 3532-3533, 1998.

2\. \"Metal Activation of Enzymes in Nucleic Acid Biochemistry.\" Chem.
Rev. 98, 1067-1088, 1998.

3\. \"Efficient Catalytic Cleavage of DNA Mediated by
Metalloaminoglycosides. Demonstration of Hydrolytic and Oxidative
Pathways\". Chem. Soc. Chem. Commun. 1737-1738, 1998.

4\. \"Chemistry of Nitric Oxide with Protein-bound Iron Sulfur Centers.
Insights on Physiological Reactivity\" J. Am. Chem. Soc. 121, 4093-4100,
1999.

5\. \"Novel Reagents for Targeted Cleavage of RNA Sequences. Towards a
New Family of Inorganic Pharmaceuticals.\" Chem. Soc. Chem. Commun.
1147-1148, 1999.

6\. \"Protein-Bound Iron-Sulfur Centers. Form, Function, and Assembly\"
Coordn. Chem. Rev. 190-192, 1049-1066, 1999.

7\. \"Competitive Binding in Magnesium Coordination Chemistry: Water
versus Ligands of Biological Interest.\" J. Am. Chem. Soc. 121,
7665-7673, 1999.

8\. \"Metal-Ion Stoichiometry of the HIV-1 RT Ribonuclease H Domain.
Evidence for Two Mutually Exclusive Sites Leads to New Mechanistic
Insights on Metal-Mediated Hydrolysis in Nucleic Acid Biochemistry\" J.
Biol. Inorg. Chem. 5, 67-74, 1999.

**Barbara Y. Croft, PhD, Program Director, Biomedical Imaging Program,
NCI.** After 29 years as a imaging physicist in the Radiology Department
at the University of Virginia, I joined the NCI Extramural program as a
Program Director in the Biomedical Imaging Program, in 1998. My
interests are in biomedical imaging, particularly in contrast agents and
the use of radioactive materials as tracers of function.

**Alvin L. Crumbliss, PhD, Professor, Chemistry, Duke University.**
Professor Crumbliss has been a member of the Duke Univ. Chem. Dept.
since 1970, where he is currently Professor. He has held visiting
faculty positions at the Université Paris - Orsay (1978, 1985, 1989),
Oxford University (1985), Ecole Européenne des Hautes Etudes des
Industries Chimiques de Strasbourg (1995), Ecole Nationale Superieure de
Chimie de Paris (1995), and Université J. Fourier de Grenoble (1996,
1999). He was the Swiss Universities Troisieme Cycle Lecturer in
Inorganic Chemistry in 1999. Honors include a NATO Senior Scientist
Fellowship (1978), Duke University Scholar - Teacher of the Year (1987),
and a twelve month research professorship award co-sponsored by the
French Academy of Science, Centre National de la Recherche Scientifique,
and Elf. -Aquitaine (Professeur de l\'Académie, 1995). Professor
Crumbliss\' research has emphasized the role of metals in biological
systems, and their speciation and mobility. Current externally funded
(NSF, NIH, ACS/PRF, Burroughs-Wellcome) research projects include the
development of chemical models for iron transport and storage in
microbial and mammalian systems, studies of metal - protein
interactions, and metallo-protein electron transfer processes, including
cooperativity in these processes.

Three recent relevant publications are as follows:\
1. \"The Coordination Chemistry of Siderophores: Thermodynamics and
Kinetics of Iron Chelation and Release\" A.-M. Albrecht-Gary and A. L.
Crumbliss, Metal Ions in Biological Systems, 35, 239 (1988).\
2. \"Conformational Fluctuations in Deoxy Hemoglobin Revealed as a Major
Contributor to Anionic Modulation of Function Through Studies of the
Oxygenation and Oxidation of Hemoglobin Ao and Hemoglobin Deer Lodge\"
C. Bonaventura, S. Tesh, K. M. Faulkner, D. Kraiter, and A. L.
Crumbliss. Biochem., 37, 496 (1998).\
3. \"Hypothesis: Iron Chelation Plays a Vital Role in Neutrophilic
Inflammation\" A. J. Ghio, C. A. Piantadosi and A. L. Crumbliss,
BioMetals, 10, 135 (1997).

**Valeria Culotta, PhD, Associate Professor, Department of Environmental
Health Sciences, Johns Hopkins University.**

Research interests: Using the bakers yeast S. cerevisiae as a model
system, we have uncovered new genes involved in metal trafficking and
transport. Included in this list are the family of \'metallochaperones\'
that act to escort copper to distinct cellular localizations and
facilitate the incorporation of the copper co-factor into copper
requiring enzymes. These proteins are highly conserved throughout
eukaryotes and may have important implications regarding human diseases
such as ALS and Wilson and Menkes disorders.\
Selected Publications:\
1. Culotta, V. C., Klomp, L., Strain, J., Casareno, R., Krems, B. and
Gitlin, J. D. The copper chaperone for superoxide dismutase. J. Biol.
Chem. 272:23469-23472, 1997.\
2. Lin, S. J., Pufahl, R., Dancis, A., O\'Halloran, T. V. and Culotta,
V. C. A role for the Saccharomyces cerevisiae ATX1 gene in copper
trafficking and iron transport. J. Biol. Chem. 272:9215-9220, 1997.\
3. Pufahl, R., Singer, C., Peariso, K. L., Lin, S. J., Schmidt, P.,
Fahrni, C., Culotta, V. C., Penner-Hahn, J. E. and O\'Halloran, T. V.
Metal ion chaperone function of the soluble Cu(I) receptor Atx1.
Science. 278:853-856, 1997.\
4. Corson, L. B., Strain, J., Culotta, V. C. and Cleveland, D. W.
Chaperone-facilitated copper binding is a property common to several
classes of familial amyotrophic lateral sclerosis-linked superoxide
dismutase mutants. Proc. Natl. Acad. Sci. USA. 95:6361-6366, 1998.\
5. Rae, T. D., Schmidt, P. J., Pufhal, R. A., Culotta, V. C. and
O\'Halloran, T. V. Undetectable intracellular free copper: the
requirement of a copper chaperone for superoxide dismutase. Science.
284:805-808, 1999.\
6. O\'Halloran, T. V. and Culotta, V. C. Metallochaperones: an
intracellular shuttle service for metal ions. J. Biol. Chem. 275:in
press, 2000.

**Dory Cwikel, PhD, visiting research staff member, Chemistry
Department, Princeton University.** Education: Maitrise es Sciences,
Faculte des Sciences, Paris, France (1968). M.Sc., Weizmann Institute,
Israel (1971). Ph.D., Technion, IIT, Israel (1987) \[selective
anti-tumour reagents: cis-platinum linked to estrogens and
metalloimmunoassays\]. Post-doctoral fellowship: Princeton University
(1986-87): \[UVRR spectroscopy of cis-platinum nucleotides complexes\].
Research experience: Chai-Tech Ltd, Technion: development of a family of
antiinflammatory and antiviral cobalt(III) Schiff base complexes (CTC
compounds) and preliminary studies of their use as protein inhibitors;
study of the interactions of macrocyclic compounds with myoglobin
(1986-94). Smoler Center for protein analysis, Technion (1994-95).
Department of Cell Biology and Immunology, Tel-Aviv University and
Medis-El R&D, Jerusalem: detection of neoplasia by polarisation of
fluorescence of lymphocytes after stimulation by antigens (1997-98).
Department of Chemistry, Technion: characterization of intermediates in
organometallic sythesis (1999). Department of Chemistry, Princeton
University: RR spectroscopic studies of vitamin B12.\
Publications:\
1. M. Cais, D. Cwikel, I. Agmon and M.Kapon: Structure of
Pt(II)-dichloro-diamino carboxylic acid complexes, XXIVth ICCC, Athens,
August 24-29, 1986, E3-820.\
2. J.R. Perno, D. Cwikel and T.G. Spiro: UVRR study of deoxyguanosine
mono phosphate and its complexes with cis-(NH3)2Pt2+, Ni2+, and H+,
Inorg. Chem., 26,1987,400.\
3. O. Blum, A. Haiek, D. Cwikel, Z. Dori, T.J. Meade and H. Gray:
Isolation of a molten globule by selective Cobalt (III) unfolding, Proc.
Natl.Acad. Sci. USA, 95,1998,6659.

**Mindy I. Davis, Graduate Research Assistant, Department of Chemistry,
Stanford University.** EDUCATION: Massachusetts Institute of Technology,
B.S. in Chemistry, 1991-1995. Stanford University, working towards Ph.D.
in Chemistry, 1995-present. RESEARCH INTERESTS: I am a graduate student
working in the lab of Professor Edward I. Solomon. My current research
interests include spectroscopic and theoretical investigation of the
mononuclear non-heme iron active sites of the intradiol dioxygenases,
extradiol dioxygenases, and bleomycin in order to obtain insight into
their reactivities. HONORS/AFFILIATIONS: Sigma Xi, Kodak Scholar, Merck
Index Award, Alpha Chi Sigma and American Chemical Society.

PUBLICATIONS:\
(1) S. P. Watton, M. I. Davis, L. E. Pence, J. Rebek, Jr., and S. J.
Lippard. \"Alkali Metal-Responsive Geometric and Spectral Changes in a
Cobalt(II) Complex of a Constrained Dicarboxylate: a Carboxylate
Shift-Mediated Metallochromoionophore.\" Inorg. Chim. Acta 1995, 235,
195-204.\
(2) M. I. Davis, E. C. Wasinger, T. E. Westre, J. M. Zaleski, A. M.
Orville, J. D. Lipscomb, B. Hedman, K. O. Hodgson and E. I. Solomon.
\"Spectroscopic Investigation of Reduced Protocatechuate
3,4-Dioxygenase: Charge Induced Alterations in the Active Site Iron
Coordination Environment.\" Inorg. Chem. 1999, 38, 3676-3683.\
(3) E. I. Solomon, T. Brunold, M. I. Davis, J. N. Kemsley, S.-K. Lee, N.
Lehnert, F. Neese, A. J. Skulan, Y.-S. Yang and J. Zhou. \"Geometric and
Electronic Structure/Function Correlations in Non-Heme Iron Enzymes.\"
Chem. Rev. 2000, 100, 235-349.

**Jeffery T. Davis, PhD, Chemistry and Biochemistry, University of
Maryland. I**nterested in nucleobase-metal interactions, particularly
G-quartet studies. For example:

1\. \"Cation Templated Self-Assembly of a Lipophilic Deoxyguanosine: The
Solution Structure of a K+-dG8 Octamer.\" Allison L. Marlow, Elisabetta
Mezzina, Gian Piero Spada, Stefano Masiero, Jeffery T. Davis and
Giovanni Gottarelli, J. Org. Chem, 1999, 64, 5116-5123.\
2. \" Binding Cesium Ion with Nucleoside Pentamers. Templated
Self-Assembly of an Isoguanosine Decamer.\" Mangmang Cai, Allison L.
Marlow, James C. Fettinger Daniele Fabris, Tamara J. Haverlock, Bruce A.
Moyer and Jeffery T. Davis, Angewandte Chemie Int. Ed., Engl., 2000, in
press.\
3. \"Towards Artificial Ion Channels: A Lipophilic G-Quadruplex.\" Scott
L. Forman, James C. Fettinger, Silvia Pieraccini, Giovanni Gottarelli
and Jeffery T. Davis, J. Am. Chem. Soc., 2000, in press.

**Kenneth J. Dillon, PhD, President, Spectrum Bioscience, Inc..**
Kenneth J. Dillon has invented Micromin transdermal micronutrition
technology and Ultramin oral controlled-release technology. Micromin is
a bracelet that operates by means of electrochemistry to deposit
minerals on the skin. Its main target is treating the neurological
symptoms of iron-deficient people. It can be used for zinc therapy as
well. Micromin is in prototype and has IND status. Ultramin is a Gastric
Delivery System technology for micromineral supplementation that also
has potential as a platform for dispensing certain drugs. The Spectrum
Bioscience Website\--biophoton.com\--describes the various features of
Micromin in the context of a Theory of Transdermal Micronutrition.

**Dabney W. Dixon, PhD, Professor of Chemistry, Department of Chemistry,
Georgia State University.** Current research interests: 1) Porphyrin and
metalloporphyrin chemistry. Porphyrins and metalloporphyrins are being
investigated as potential agents against both bacteria and viruses
involved in sexually transmitted diseases. 2) Heme uptake in pathogenic
bacteria. The binding of natural porphyrins and metalloporphyrins to
proteins involved in heme uptake in pathogenic bacteria is being studied
to elucidate the binding sites for heme and mechanisms of heme uptake.
3) Intercalator binding to DNA. Comparisons of the on and off rates of
intercalator binding to DNA yield information about the kinetic and
thermodynamic factors which control this binding. 4) Cleavage of abasic
sites in DNA. Polyamines and intercalator -amines can be efficient
cleavers of the DNA backbone at abasic sites. We are studying the
mechanism of this reaction.

**Susan R. Doctrow, PhD, Vice President, Research, Eukarion, Inc..**

Selected publications relevant to the conference:\
1. Gonzalez, P.K., Zhuang, J., Doctrow, S.R., Malfroy, B., Benson, P.F.,
Menconi, M.J., and Fink, M.P. EUK-8, a synthetic superoxide dismutase
and catalase mimetic, ameliorates acute lung injury in endotoxemic
swine. 1995. Journal of Pharmacology and Experimental Therapeutics 275:
798-806\
2. Doctrow, S.R., Huffman, K., Marcus, C.B., Musleh, W., Bruce, A.,
Baudry, M., and Malfroy, B. \"Salen manganese complexes: combined
superoxide dismutase/catalase mimics with broad pharmacological
efficacy\" in Antioxidants in Disease Mechanisms and Therapeutic
Strategies. (H. Sies, ed.). 1996. Advances in Pharmacology 38: 247-269.\
3. Malfroy, B., Doctrow, S.R., Orr, P.L., Tocco, G., Fedoseyeva, E.V.,
and Benichou, G. Prevention and suppression of autoimmune
encephalomyelitis by EUK-8, a synthetic catalytic scavenger of oxygen
reactive metabolites. 1997. Cellular Immunology 177:62-68.\
4. Gonzalez, P.K., Doctrow, S.R., Malfroy, B., and Fink, M.P. Role of
oxidant stress and iron delocalization in acidosis-induced intestinal
epithelial hyperpermeability. 1997. Shock 8:108-114.\
5. Baker, K., Bucay Marcus, C., Huffman, K., Kruk, H., Malfroy, B., and
Doctrow, S.R. Synthetic combined superoxide dismutase/catalase mimics
are protective as a delayed treatment in a rat stroke model: a key role
for reactive oxygen species in ischemic brain injury. 1998. Journal of
Pharmacology and Experimental Therapeutics 284:215-221.\
6. Rong, Y., Doctrow, S.R., Tocco, G., and Baudry, M. EUK-134, a
synthetic superoxide dismutase and catalase mimetic, prevents oxidative
stress and attenuates kainate-induced neuropathology. 1999. Proc. Natl.
Acad. Sci. (USA) 96:9897-9902.

**Tom Dowell, PhD, HSA, CSR, NIH.** SRA, Alcohol & Toxicology,
Subcommittee 1

**Francis D\'Souza, PhD, Associate Professor, Chemistry, Wichita State
University.** B. Sc. and M. Sc. degrees from the University of Mysore,
India (1982 and 1984) and the Ph. D. degree from the Indian Institute of
Science, Bangalore, India (1992) under the direction of Professor V.
Krishnan. After graduation, he worked as a Research Associate in the
laboratory of Professor Karl M. Kadish, University of Houston, Houston
(1992-94). He was also a Research Scientist at the Université de
Bourgogne, Dijon, France (1993) and a visiting researcher at the
Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw,
Poland (1997 and 1999). The Ph. D. thesis of Dr. D\'Souza was related to
inter- and intramolecular electron transfer in porphyrin donor-acceptor
molecules. As a research associate at the University of Houston, Dr.
D\'Souza was involved in the synthesis, electrochemical and spectral
characterization of non-planar porphyrins, structural isomers of
porphyrin, such as porphycene and corphycene, and fullerene
electrochemistry including the electrosynthesis of organofullerene
derivatives. At Wichita State University, he has been leading his
research group for the last six years in order to develop porphyrin
receptors capable to form non-covalently bound supramolecular complexes
via molecular recognition route. These supramolecular systems are
primarily designed for developing chemosensor,s and, for modification of
the electrode surface for sensor applications. He has co-authored nearly
60 publications in peer-reviewed journals and has given over 50
presentations at the national and international meetings in the brief
period of his academic career.\
Publications\
1. D\'Souza, F.; Deviprasad, G. R.; Rahman, M. S.; Choi, J.-p Inorg.
Chem., 1999, 38, 2157.\
2. Deviprasad, G. R.; Rahman, M. S.; D\'Souza, F. Chem. Commun. 1999,
849.\
3. D\'Souza, F.; Choi, J.-p.; Kutner, W J. Phys. Chem. B. 1999, 103,
2892.\
4. D\'Souza, F., Deviprasad, G. R. Hsieh, Y.-Y. Chem. Commun. 1998,
1027.\
5. D\'Souza, F. Choi, J.-p.; Kutner, W. J. Phys. Chem. 1998, 102, 4247.\
6. Deviprasad, G. R.; Keshavan, B.; D\'Souza, F. J. Chem. Soc., Perkin
Trans. 1, 1998, 3133.\
7. D\'Souza, F., Deviprasad, G. R. Hsieh, Y.-Y. Chem. Commun. 1997,
533.\
8. D\'Souza, F.; Hsieh, Y.-Y.; Wickman, H.; Kutner, W Chem. Commun.,
1997, 1191.\
9. D\'Souza, F. J. Am. Chem. Soc., 1996, 118,

**Kim R. Dunbar, PhD, Professor of Inorganic Chemistry, Chemistry, Texas
A&M University.**

B.S. Chemistry, Westminster College, 1980; Ph.D. Inorganic Chemistry,
Purdue University, 1984 with R.A. Walton; Postdoctoral Research
Assistant with F.A. Cotton at Texas A&M University, 1985-1986. Faculty
Member at Michigan State University, 1987-1999. Distinguished Professor
of Chemistry Michigan State University 1998-99. Professor of Chemistry,
Texas A&M University, 1999. Fellow of the Alfred P. Sloan Foundation and
Henry and Camille Dreyfus Foundation. Chair of the 1999 Gordon Research
Conference on Inorganic Chemistry. Author of 130 publications in the
general area of transition metal chemistry with specific projects in the
synthesis and reactivity of organometallic compounds, magnetic behavior
of coordination compounds and the study of metal binding to nucleic
acids.

**Joseph E. Earley, PhD, Program Officer, Inorganic, Bioinorganic and
Organometallic Chem., National Science Foundation.** IBO-CHE at NSF.
Also, Professor Emeritus (Inorganic Chemistry) Georgetown University.
Research Interests: Rates and mechanisms of inorganic reactions in
aqueous solution, Catalysis of inorganic redox reactions by molecular
recognition, Kinetics and mechanisms of ruthenium(III)-titanium(III)
electron-transfer reactions. Non-local effects on coupled chemical
oscillators. Postdoctoral Research with: Henry Taube, Harry B. Gray,
Ilya Prigogine, Yoichi Sasaki.\
Recent publications:\
a) Titanium(III)-Ruthenium(III) Electron Transfer Through
3,6-Dihydroxy-1,4-benzoquinonate Ligands:An Ultra-short Insulated
Wire.Inorg. Chem 1999, 18, 4128-4131.\
b) Synthesis of the
{Co\[(6-amino-6-(4-aminobenzyl)-1,4,8,11-tetra-azacyclotetradecane\]PO4},
a potential phosphate-binding site for molecular recognition. Inorganica
Chemica Acta.293 (1999) 245-247;\
c) A Novel Tetrazamacrocylic Ligand: Metal-Directed Synthesis, and
Characterization of CoIII and CuII Complexes; Inorganica Chemica
Acta.288 (1999), 40-46.\
d) Naturalism, Theism, and the Origin of Life. Sr. Process Studies,
27:3-4, (1998), 267-279\
e) Modes of Chemical Becoming, Joseph E. Earley, Hyle, 4(2), 1998.
http://rz70.rz.uni-karlsruhe.de/\~ed01/Hyle/Hyle4/earley.htm I

**Richard C. Elder, PhD, Professor, Chemistry, Biomedical Chemistry
Research Center, University of Cincinnati.** PhD MIT (F.A.Cotton) 1964,
Postdoc 1964-1965; Instructor,Assistant Prof. U. Chicago 1965-1970;
Associate Prof, Professor U. Cincinnati, OH; Structural Inorganic
Chemistry, Xtallography, EXAFS, X-ray Scattering from Solutions,
Metal-Based Drugs, Gold Antiarthritis Drugs and Metabolites,
Dicyanogold(I) anion as an antiHIVDrug, Cisplatin and Biotransformation
Products, ICP-MS as an Element Specific Detector for HPLC.

**Jeff Ellison, PhD, Staff Scientist Inorganic Chemistry, EPIX Medical,
Inc.** Jeff Ellison has been with EPIX since 1997. He came from a
postdoc with Julia Kovacs, investigating the role of iron in nitrile
hydratase enzymes. He earned his doctorate with Phil Power, studying the
kinetic stabilization of low-coordinate metal environments. He recently
coauthored a review of gadolinium chelates as MRI contrast agents (Chem.
Rev., 1999,99,2293).

**Billy Joe Evans, PhD, Professor of Chemistry, Department of Chemistry,
University of Michigan.** Interested in biomineralization and signal
transduction between inanimate material and living tissue and the
relationship of these to magnetism.

**Greg L. Evans, PhD, Program Administrator, Blood Diseases Program,
NHLBI.** Oversee basic science grant portfolio in sickle cell disease
for NHLBI; interested in imaging agents for vascular disease, anything
related to metal chelation (re iron overload in sickle disease), also
nutritional supplements of other metals (zinc, magnesium)for treatment
of blood diseases

**Ramy S. Farid, PhD, Assistant Professor, Department of Chemistry,
Rutgers University.** Ph.D. 1991, California Institute of Technology
(advisor: Harry Gray); NIH Postdoctoral Fellow 1991-1993, University of
Pennsylvania (with P. Leslie Dutton); Assistant Professor of Chemistry
1994-present, Rutgers, The State University of New Jersey, Newark
Campus. Research Interests: The focus of my research has been
understanding the role that protein medium plays in controlling
biological electron transport. More recently my research has focused on
the de novo design and synthesis of stable metalloproteins suitable for
electron-transfer studies as well as studies aimed at understanding the
role that protein plays in controlling metal mediated catalytic
reactions. We have developed a new computer program called CORE that
determines amino acid sequences predicted to stabilize a target protein
structure. With this program we have designed several highly stable
synthetic proteins: (1) a protein that binds heme groups in a
perpendicular arrangement mimicking the heme a/a3 orientation found in
cytochrome c oxidase, (2) a protein capable of converting light energy
into a long-lived charge-separated state via rapid photoinduced electron
transfer from a bis-histidine bound Ru(bpy)2 group to a bis-histidine
bound heme group, (3) a protein that binds catalytically active square
planar rhodium complexes via phosphite modified tyrosine residues.

1\. X. Jiang, H. Farid, E. Pistor, R. S. Farid \"A new approach to the
design of uniquely\
folded thermally stable proteins\" Protein Science 2000, 9, 403-416.\
2. X. Jiang, E. Bishop, R. S. Farid \"A de novo Designed Protein with
Properties that\
Characterize Natural Hyperthermophilic Proteins\" J. Am. Chem. Soc.
1997, 119, 838-839.

**Walt Fast, PhD, Postdoctoral Fellow, Chemistry, The Pennsylvania State
University.** Walt Fast is a NIH postdoctoral fellow in the laboratory
of Prof. Stephen Benkovic and is currently using site-directed
mutagenesis and pre-steady-state kinetics to determine the kinetic and
chemical mechanism of a zinc-dependent beta-lactamase. His graduate
studies were with Richard B. Silverman (Northwestern Univ.) and involved
designing, synthesizing, and determining the mechanism of action for
mechanism-based inactivators of nitric oxide synthase. Selected refs:

1\. Fast, W., Nikolic, D. Van Breemen, R.B., Silverman, R.B. J. Am.
Chem. Soc. 1998, 121, 903-916.;

2\. Wang, Z., Fast, W. Benkovic, S.J. Biochemistry 1999, 38,
10013-10023.

**Bill R. Foster, MD, Senior Staff Physician, OD/OSPPA, NIH/NIDDK.**
M.S. in Biochemistry, with M.D. Post-doctoral fellowship in
Physiological Chemistry. Co-Author of textbook on nutrition

**Bruce A. Fowler, PhD, Director, Program in Toxicology, Toxicology,
University of Maryland.** Bruce A. Fowler, Ph.D., Fellow, A.T.S. is
Director, Program in Toxicology and Professor of Pathology the
University of Maryland School of Medicine. He has served on a number of
committees of the NAS/NRC and is the current chairman of the Scientific
Committee on the Toxicology of Metals under the International Commission
on Occupational Health. He has a career - long interest in mechanisms of
metal toxicity, metal-induced alterations in the heme biosynthetic
pathways, metal-induced alterations in gene expression and roles of
metal binding proteins in mediating toxicity in mammals and aquatic
organisms. Publications: Conner, E.A., Yamauchi,H. and Fowler,B.A.:
Alterations in the heme biosynthetic pathway form the III-V
semiconductor metal, indium arsenide(InAs). Chem. Biol. Interact.
96:273-285, 1995; Bustamente, Dock,L., Vahter, M., Fowler, B.A. and
Orrenius,S. The semiconductor elements arsensic and indium induce
apoptosis in rat thymocytes. Toxicology 118: 129-136, 1997.; Smith,
D.R., Khang, M.W., Quintanilla-Vega, B. and Fowler, B.A. High affinity
renal lead-binding proteins in environmentally exposed humans. Chem.
Biol. Interact. 115:39-52, 1998.

**Christopher J. Frederickson, PhD, Professor, Anatomy & Neuroscience,
Biomedical Engineering, University of Texas Medical Branch.** Dr.
Frederickson is CEO of NeuroBioTex, Inc. and Professor and Senior
Scientist in Anatomy and Neuroscience, and Biomedical Engineering at The
UT-Medical Branch, Galveston TX. He is the co-discoverer of neurons that
store and release zinc ions from synaptic boutons (zinc-containing
neurons) and inventor of the reference standard histochemical method for
zinc (TSQ-Molecular Probes). Frederickson edited \"The Neurobiology of
Zinc,\" vol A and B (AR Liss) and was the chair of a recent NIH
Symposium session on \"Zinc in the Brain\" (J Nutrition, 2000, in
press). He has published over 60 research and invited review articles on
zinc neurobiology.

**Paul R. Gardner, PhD, Research Assistant Professor, Critical Care
Medicine, Children\'s Hospital Research Foundation.** B.S. Biochemistry,
1984, Ohio State University; Ph.D. Biochemistry, 1990, Duke University;
Metal ion interactions with nitric oxide, superoxide, and dioxygen.
Targets, actions and metabolism of nitric oxide and superoxide in
bacteria and mammals. 1) \"Nitric oxide dioxygenase: an enzymic function
for flavohemoglobin\" Proc. Natl. Acad. Sci. USA 1998, 95, 10378. 2)
\"Steady-state and transient kinetics of the Escherichia coli nitric
oxide dioxygenase (flavohemoglobin): The B10 Tyrosine hydroxyl is
essential for dioxygen binding and catalysis\" J. Biol. Chem. 2000, 275,
12581. 3) \"Nitric oxide sensitivity of the aconitases\" J. Biol. Chem.
1997, 272, 25071. 4) \"Superoxide-driven aconitase Fe-S center cycling\"
Biosci. Rep. 1997, 17, 33-41. 5) \"Superoxide scavenging by Mn(II/III)
tetrakis (1-methyl-4-pyridyl) porphyrin in mammalian cells\". Arch.
Biochem. Biophys. 1996, 325, 20.

**Hilary Arnold Godwin, PhD, Assistant Professor, Department of
Chemistry, Northwestern University.** I am currently an Assistant
Professor in the Department of Chemistry at Northwestern University,
with a joint appointment in the Department of Biochemistry, Molecular
Biology, and Cell Biology. Prior to my appointment at Northwestern
(1996), I conducted postdoctoral research on zinc finger proteins in the
laboratory of Professor Jeremy Berg in the Department of Biophysics and
Biophysical Chemistry in the Johns Hopkins University School of Medicine
(1994-1996). I received my Ph.D. (1994) in Physical Chemistry from
Stanford University. My thesis research was on the subject of
heterometallic metal-metal multiple bonds and was performed under the
guidance of Professor James P. Collman. The primary focus of the
research in my laboratory at Northwestern is to elucidate the molecular
mechanism of lead poisoning. Towards this end, we are studying how
tightly lead binds to proteins that have been implicated in lead
poisoning and how lead affects the structure and dynamics of these
targets. Other research interests in my laboratory include studying the
fundmamental aqueous coordination chemistry and spectroscopic properties
of Pb(II), designing new chelating agents and fluorescent sensors for
Pb(II), and studying the affects of Pb(II) on microorganisms. In
addition, we are studying the molecular mechanism of calcium mediated
neurotransmission and how lead affects this process.\
Recent publications from my laboratory include:\
1. \'Lead-Fingers: Pb(II)-Binding to Structural Zinc-Binding Domains
Determined Directly By Monitoring Lead-Thiolate Charge Transfer Bands\'
Payne, J. C.; ter Horst, M. A.; Godwin, H. A. J. Am. Chem. Soc., 1999,
121, 6850-6855.\
2. \'A Selective, Ratiometric, Fluorescent Sensor for Pb2+\' Deo, S.;
Godwin, H. A. J. Am. Chem. Soc., 2000, 122, 174-175

3\. \'207Pb-1H Two-Dimensional NMR Spectroscopy: A Useful New Tool For
Probing Lead(II) Coordination Chemistry\' Claudio, E. S.; ter Horst, M.
A.; Forde, C. E.; Stern, C.; Zart, M. K.; Godwin, H. A. Inorg. Chem. In
press. (This article can be downloaded at the following site:
<http://pubs.acs.org/cgi-bin/doilookup?10.1021/ic9909>.

**Radoslav Goldman, PhD, Research Instructor, Lombardi Cancer Center,
Georgetown University.**

1\. Faculty member, FAES graduate school at the National Institutes of
Health, Instructor in graduate level Biochemistry course,
01.1999-01.2000. 2. Molecular Epidemiology Section, LHC/NCI/NIH, Dr. P.
G. Shields, 1996-present. Development of methods for detection of
DNA-adducts : 14C postlabeling with AMS detection, capillary HPLC-LIF,
CE-LIF of IgG complexes, mass spectrometry . High throughput assay of
helicase activity based on FRET of fluorescently labeled
oligonucleotides. Application of the analytical methods to molecular
epidemiology of lung and breat cancer. 3. University of Pittsburgh,
Pittsburgh, EOH-GSPH, Dr. V. E. Kagan, 1993-1996. Studies on the
toxicity of phenolic compounds mediated by redox-cycling of phenoxyl
radicals. 4. GSF Research Center, Institut fur Strahlenbiologie, Dr. W.
Bors, summer 1995. Pulse radiolytic determination of rate constants of
reactions involving phenoxyl radicals. 5. University of Michigan, Ann
Arbor, Dept. of Chemistry, Professor M. Koreeda, 1993. Synthesis of
vinylsilanes and siloenolethers, Sharpless asymmetric dihydroxylation,
IR, NMR. 6.. University of Michigan, Department of Medicinal Chemistry,
Professor M. A. Marletta, 1992. Hydride transfer from NADPD to nitric
oxide synthetase, lithium inhibition of guanylate cyclase. 7. University
of Michigan, Department of Biochemistry, Dr. P. C. Andrews, 1991-1992.
Separation of proteins in human perilymph using one and two dimensional
gel electrophoresis. 8. Genentech Inc., South San Francisco, CA,
Cardiovascular Dept., Dr. R. Thomas, 1991. Physiological model of
hypotensive shock and its prevention in the rat using C1-inhibitor. 9.
University of California, Berkeley, Membrane Bioenergetics Group,
Professor L. Packer, 1990. Mechanism of reduction of vitamin E radical
by ascorbic acid using EPR, HPLC, and UV-Vis.

PUBLICATIONS:\
1. Goldman, R., Day, B. W., Carver, T. A., Mauthe, R. J., Turteltaub, K.
W., and Shields, P. G. (2000) Quantitation of carcinogen-DNA adducts by
14C-postlabeling methods. Chemico-Biological Interactions, in press\
2. Goldman, R., Claycamp, H. G., Sweetland, M. A., Sedlov, A., Kisin, E.
R., Tyurina, Y. Y., Ritov, V. B., Wenger, S. L., Grant, S. G., and
Kagan, V. E. (1999) Myeloperoxidase-catalyzed redox-cycling of phenol
promotes lipid peroxidation and thiol oxidation in HL-60 cells. FRBM,
27, 1050-1063\
3. Goldman, R., and Shields, P. G. (1998) Molecular epidemiology of
breast cancer. In Vivo, 12, 43-48\
4. Goldman, R., Tsyrlov, I. B., Grogan, J., and Kagan, V. E. (1997)
Reactions of phenoxyl radicals with NADPH-cytochrome P-450
oxidoreductase and NADPH : reduction of the radicals and inhibition of
the enzyme. Biochemistry, 36, 3186-3192\
5. Goldman, R., Bors, W., Michel, C., Day, B. W., and Kagan, V. E.
(1997) Environmental and nutritional phenols : bioactivation to phenoxyl
radicals and their cytotoxic interactions with intracellular reductants.
Environmental & Nutritional Interactions, 1, 97-118\
6. Goldman, R., Stoyanovsky, D. A., Day, B. W., and Kagan, V. E. (1995)
Reduction of phenoxyl radicals by thioredoxin results in selective
oxidation of its SH-groups to disulfides. An antioxidant function of
thioredoxin. Biochemistry, 34, 4765-4772

**Kathryn B. Grant, PhD, Assistant Professor of Biochemistry, Department
of Chemistry, Georgia State University.** B.A., 1980, New York
University; B.S., 1989, SUNY at Purchase; Ph.D., 1994, Columbia
University (advisor: Koji Nakanishi); NIH Postdoctoral Fellowship,
1994-1997, California Institute of Technology (advisor: Peter B.
Dervan); 1997 - present, Assistant Professor of Biochemistry, Georgia
State University; 2000 - 2004 NSF CAREER Award; Research Interests:
development of combinatorial strategies to facilitate the discovery of
metal ions and complexes for peptide cleavage; genetic analyses of
molecular mechanisms that contribute to antidepressant drug resistance
in major depressive disorder.

**Trevor W Hambley, PhD, Associate Professor, School of Chemistry,
University of Sydney.**

Research Interests: Pt/DNA Interactions, Mechanism of action of Pt
drugs, Design of new Pt complexes, Toxicity of Pt complexes. Metal
complexes of anti-inflammatory drugs, Matrix Metalloproteinase
inhibitors, Molecular modelling, crystallography

**Wesley R. Harris, PhD, Professor of Chemistry, Chemistry, University
of Missouri-St. Louis.**

1988-present. Current Research Interests: (1) Mechanism of iron removal
from serum transferrin. Includes mechanistic studies on the
conformational gating of iron release and on the allosteric effects of
anions on the rate of iron release. This project also includes the
design and synthesis of low molecular weight ligands designed to
accelerate iron release. (2) Complexation of Aluminum in blood. We have
conducted equilibrium studies on the binding of the aluminum(III) ion to
both transferrin and to low molecular weight chelating agents found in
blood. We are currently working on a new computer model for the
speciation of Al in serum. (3) Metal binding to FbpA. We are initiating
new studies on the binding of trivalent metal ions to the bacterial
periplasmic iron transport protein known as FbpA. This is a
transferrin-like protein that utilizes phosphate in place of carbonate
as a synergistic anion for metal binding. Relatively little is known
about its metal binding affinities. We are interested in binding of
metals such as Al(III), Ga(III) and In(III).

**Maureen N. Hood, Research Coordinator, Diagnostic Radiology, Warren G
Magnuson Clinical Center.** Research Coordinator with background in
Nursing and MRI. Current research is in Magnetic Resonance,
predominantly cardiovascular. Research ranges from clinical trials with
new contrast agents to pulse sequence development. Publications:

1\. Hood,Ho,Smirniotopoulos,Szumowski. Chemical Shift: The Artifact and
Clinical Tool Revisited. RadioGraphics 1999;19:357-371.\
2. Ho,Choyke,Hood, et al.\"Automated Bolus Chase Peripheral MR
Angiography: Initial Practical Experiences and Future Directions of this
Work-In-Progress.\" JMRI 1999;10:376-388.

**Hua-Fen Hsu, PhD, Postdoctoral Fellow, Chemistry, University of
Minnesota.** I obtained my Ph.D. in 1997 in Inorganic Chemistry from the
State University of New York at Stony Brook under the guidance of
Professor Stephen Koch. My thesis project involved the chemistry of iron
thiolate complexes with CN and CO. This research has developed a series
of first relevant models for Hydrogenase. Completion of this work
resulted in 3 papers published and some are in preparation. Presently, I
am a postdoctoral fellow at the University of Minnesota under the
guidance of Professor Lawrence Que, Jr. My current projects are involved
in the chemistry of nonheme diiron enzymes and copper trafficking
proteins. I have obtained the crystal structure for a high valent diiron
compound that serves as the most relevant structural model for high
valent intermediates in nonheme diiron enzymes. The paper of this result
has been published in J. Am. Chem. Soc. recently. Other than studies of
model compounds, I have made my efforts on spectroscopic
characterization (mainly EXAFS) of alkane hydroxylase (AlkB) and Wilson
Disease protein which have resulted in one paper in Biochemistry and
another one in preparation.

**Jeffrey H. Hurst, PhD, Health Scientist Administrator, , National
Heart, Lung and Blood Institute.** Ph.D., pharmacology, Dartmouth
Medical School; Postdoctoral, neuroscience, University of Maryland;
National Research Service Award recipient, Section on Biochemical
Pharmacology, NHLBI; Health Scientist Administrator, NLHBI. Research
interests include blood and vascular diseases, basic and clinical
neurology, drug development, pharmacognosy, drug receptors.

**Hiroshi H. Ishida, PhD, Research Scientist, Experimental Therapeutics,
NCI.** I have been working on botulinum toxin\'s inhibitory effect on
neuroexocytosis in PC12 cells for 2 years to develop a countermeasures
against the toxin. The toxin has a Zn-dependent peptidase activity nad
could prevent the effect by usilng metals.

**Sandra D. Jones, Clinical Research Nurse, Imaging Sciences Program,
Diagnostic Radiology, Clinical Center.** RN, MS; Interests: mental
health, aging and alcohol; and imaging sciences (magnetic resonance
imaging; computed tomography; special procedures)

**Chu W. Jung, PhD, Scientist, VPE Scientific.** Formerly Senior
Scientist and Head of MRI Laboratory at Advanced Magnetics, Inc.
Research interests: magnetite nanoparticle physics and chemistry;
sentinel lymph node and tumor perfusion imaging with nanoparticles.
Previously was at Dow Chemical\'s Central Research Lab in Wayland, MA.
where he prepared the first Starburst (dendrimer) MRA contrast agents in
1986.

**Igor A. Kaltashov, PhD, Assistant Professor, Chemistry, University of
Massachusetts.**

Education: Moscow Institute of Physics and
Technology,M.S.(1989,Physics); University of Maryland Baltimore
County,Ph.D.(1996,Chemistry); Johns Hopkins University School of
Medicine, Post-doc(1995-1997). Recent affiliations: 1997-1999,University
of Massachusetts, Lecturer and Director of Mass Spectrometry Center.
Current research interests: Biological applications of mass
spectrometry; Protein dynamics and binding; Architecture and dynamics of
metalloproteins.

Representative recent publications:\
1. S.J. Eyles, P. Speir, G. Kruppa, L.M. Gierasch, I.A. Kaltashov.
Protein conformational stability probed by Fourier transform ion
cyclotron resonance mass spectrometry. J. Am. Chem. Soc., 2000, 122,
495-500.\
2. S.J. Eyles, T. Dresch, L.M. Gierasch, I.A. Kaltashov. Unfolding
dynamics of a beta-sheet protein studied by mass spectrometry. J. Mass
Spectrom., 1999, 34, 1289-1295.\
3. A.Li, C. Fenselau, I.A. Kaltashov. Stability of secondary structural
elements in a solvent-free environment. II: the beta-pleated sheets.
Proteins, 1998, S2, 22-27.\
4. I.A. Kaltashov, C. Fenselau. Stability of secondary structural
elements in a solvent-free environment: the alpha-helix. Proteins, 1997,
27, 165-170.\
5. I.A. Kaltashov, V. Doroshenko, R.J. Cotter, K. Takayama, N. Qureshi.
Confirmation of the structure of lipid A derived from the
lipopolysaccharide of Rhodobacter sphaeroides by a combination of MALDI,
LSIMS, and tandem mass spectrometry. Anal. Chem. 1997, 69, 2317-2322.\
6. I.A. Kaltashov, R.J. Cotter, W.H. Feinstone, G.W. Ketner, A.S. Woods.
Ferrichrome: surprising stability of a cyclic peptide-FeIII complex
revealed by mass spectrometry. J. Am. Soc. Mass Spectrom. 1997, 8,
1070-1077.

**Mijeong Kang, Grauate Student, Chemistry, Texas A&M University.** My
research topic is to study of the metal complex as a anticancer drug.
Main focus for now is on the investigation of the interaction of metal
complex with DNA. As a previous experiences, there are organic synthesis
using organometallic compounds and structure elucidation of organic
molecule by NMR.

**Kenneth D. Karlin, PhD, Professor of Chemistry, Department of
Chemistry, Johns Hopkins University.** Ira Remsen Chair in Chemistry,
The Johns Hopkins University. Postdoctoral Fellow, Cambridge University,
England, 1975-1977. Ph.D., Columbia University, New York, 1975. B.S.,
1970, Stanford University. RESEARCH INTERESTS: Inorganic and
Bioinorganic Chemistry. Bioinorganic Chemistry of Dioxygen; Structural
and Functional Models for Copper Metalloproteins. Cu(I)/Cu(II) Redox
Processes. Metal-Peroxide Chemistry; Oxidation Catalysis. Reversible
Binding of O2 and CO. Models for Hemocyanin and or Heme-Fe O2-Carriers.
O2-Reduction by Cu Cluster Compounds; Models for Copper Oxidases. Models
for Heme-Copper Oxidases. Porphyrin-Iron & Copper Complex O2-Reactivity.
NOx Chemistry; Models for Cu or Fe Nitrite, Nitrous Oxide, and Nitric
Oxide Reductases. Redox-Active Ligands and Metal Complexes;
Metal-Pterins. Hydrolysis (Amide, Peptide, Phosphate Esters) Catalyzed
by Metal Ion (e.g., Zn, Cu) Clusters. DNA or Peptide Cleavage by Copper
and Other Metal Cluster Compounds. ACTIVITIES (selected): Editor:
Progress in Inorganic Chemistry (Wiley-Interscience), 1992-present.
Petroleum Research Fund (PRF) of the American Chemical Society (ACS).
Advisory Board Member, 1998-2001. NIH Study Section: Review Panel
Member, Metallobiochemistry (BMT), 1988-1992. International Organizing
Committee: International Conference on Bioinorganic Chemistry (ICBIC).
Society for Biological Inorganic Chemistry (SBIC), Tresurer (elected),
1999-2002. 1996 Chairman (elected), Bioinorganic Subdivision, Division
of Inorganic Chemistry, American Chemical Society. Metals in Biology
Gordon Research Conference, Ventura, CA. Co-Chair, \'97; Chair, \'98.
EDITORIAL BOARDS: Journal of Inorganic Biochemistry (\'92- ), Inorganic
Chemistry (\'95-\'97), Journal of Biological Inorganic Chemistry (JBIC)
(\'96-\'99).

SELECTED PUBLICATIONS: Karlin, K. D. \"Metalloenzymes, Structural Motifs
and Inorganic Models\", Science, 1993, 261, 701-708. Murthy, N. N.;
Mahroof-Tahir, M.; Karlin, K. D., \"Facile Amide Hydrolysis Effected by
Dinuclear Copper Complexes\", J. Am. Chem. Soc., 1993, 115, 10404-10405.
Karlin, K. D.; Tyeklár, Z. \"Functional Biomimics for Copper Proteins
Involved in Reversible O2-Binding, Substrate Oxidation/Oxygenation and
Nitrite Reduction\", Advances in Inorganic Biochemistry, 1994, 9,
123-172. Karlin, K. D.; Zhu, Z-Y.; Karlin, S., \"The Environment of
Multinuclear Copper Metal Linkages in Protein Structures\", JBIC, J.
Biol. Inorg. Chem., 1998, 3, 172-187. Obias, H. V.; Lin, Y.; Murthy, N.
N.; Pidcock, E.; Solomon, E. I. Ralle, M.; Blackburn, N. J.; Neuhold,
Y.-M.; Zuberbühler, A. D.; Karlin, K. D. \"Peroxo-, Oxo-, and
Hydroxo-Bridged Dicopper Complexes: Observation of Exogenous Hydrocarbon
Substrate Oxidation\", J. Am. Chem. Soc., 1998, 120, 12960-12961.
Pidcock, E.; Obias, H. V.; Abe, Masaaki; Liang, H.-C.; Karlin, K. D.;
Solomon, E. I. \"Spectroscopic and Theoretical Studies of Oxygenated
Dicopper(I) Complexes Containing Hydrocarbon-linked
Bis\[2-(2-pyridyl)ethyl\]-amine units: Investigation of a Butterfly
\[Cu2-m-h2:h2)(O2)\]2+ Core\", J. Am. Chem. Soc., 1999, 121, 1299-1308.
Karlin, K. D.; Zuberbühler, A. D., \"Formation, Structure, and
Reactivity of Copper Dioxygen Complexes\", In Bioinorganic Catalysis:
Second Edition, Revised and Expanded. (Reedijk, J.; Bouwman, E.; Eds.),
Marcel Dekker: New York, 1999, Ch. 14, 469-534. Liang, H.-C., Dahan, M.;
Karlin, K. D. \"Dioxygen-activating bio-inorganic model complexes\",
Current Opinion in Chemical Biology, 1999, 3, 168-175. Ghiladi, R. A.;
Ju, T. D.; Lee, D.-H.; Moënne-Loccoz, P.; Kaderli, S.; Neuhold, Y.-M.;
Zuberbühler, A. D.; Woods, A.S.; Cotter, R.J.; Karlin, K. D. \"Formation
and Characterization of a High-Spin Heme-Copper Dioxygen (Peroxo)
Complex\", J. Am. Chem. Soc., 1999, 121, 98

**John V. Kelsey, Dental Team Leader, Division of Dermatologic and
Dental Drug Products, Food and Drug Administration.** I am a dentist and
a reviewer in FDA\'s Center for Drug Evaluation and Research. Our
Division has reviewed matrix metalloproteases used to treat periodontal
disesases and we anticipate submissions for similar products.

**Morris Krauss, PhD, Senior Fellow, Center Advanced Research
Biotechnology, National Institute Standards Technology.** Theoretical
calculation of the binding, electronic properties, and reactivity in
enzyme active sites. The ab initio analysis of the structure of
metalloenzyme active sites. Calculations in progress on enzymes in
shikinmate pathway (chorismate mutase, DAHP synthase), DNA repair
enzymes (UDG, HAP-1), carbonic anhydrase, glyoxalase I, and bi-metallic
enzymes (phosphotriesterase, Zinc lactamase) Earlier calculations of
binding of platinum ammines to DNA. Effective fragment potential
methodology allows treatment of many hundreds of atoms at active site
with ab initio quantum chemistry.\
Some relevant publications:\
1. Ab initio determination of the structure of the active site of a
metalloenzyme: Metal substitutions in phosphotriesterase, M.Krauss,
S.Kafafi Int.J.Quantum Chem.75,289-99(1999)\
2. Structure and spectroscopy of metallo-b-lactamase active sites,
H.S.R.Gilson and M.Krauss, J.Am.Chem.Soc. 121,6984(1999)\
3. Molecular Dynamics and Quantum Chemical Study of Endonuclease V
Catalytic Mechanism M.Krauss, R.Nirmala, N.Luo,R.Osman, ACS Symposium
Series 721 (Transition State Modeling for Catalysis) 721,424 (1999).\
4. Vanadate complex spectroscopy at the RNase A active site,
M.Krauss;B.Wladkowski, Int.J.Quant.Chem. 1998,69,11.\
5. Effective fragment potentials and the enzyme active site, S.E.
Worthington, M.Krauss, Computers Chem. in print 2000.

**Bala S. Krishnan, PhD, Sr. Principal Scientist, Discovery Analytical
Sciences, Bristol-Myers Squibb company.** 1981- present : Bristol-Myer
Squibb Company, MRI and DNA-drug interactions; 1978-81 : Post-doctoral
Fellow: DNA-drug interactions, U.of Rochester; 1975-78: Post-doctoral
Fellow, metalloenzymes SAR by ESR and NMR, Penn State U.; 1973-75 : ESR
metal complexes; 1973: Ph.D. Metal complexes NMR imaging and in-vivo
spectroscopy, drug-DNA interactions by NMR NOE distance geometry
mechanism of action of antitumor drugs, structure-activity relationships
of enzymes by NMR, structure elucidation and characterization of novel
antitumor, antiinfective antibiotic, cardiovascular and CNS compounds
for drug discovery, product development, drug metabolism and toxicology
by NMR and other analytical techiques, responsible for technical
evaluation and purchase of 11 high field NMR instruments, Bio-physical
studies (NMR, fluorescence, CD, UV-VIS, stopped-flow techniques) of
drug - DNA interactions, structure-activity relationships of glutamine
synthetase and Concanavalin A by NMR and EPR techniques, Developed new
method of analysis of platinum containing antitumor drugs by Pt-195 NMR,
Enzyme isolation and purification, enzyme kinetics, oligonucleotide
synthesis and purification, synthesis of inorganic complexes,
radioisotope labelling, interpretation of UV-VIS, IR, Fluorescence and
Circular Dichroism spectral data.\
Publications:\
1. Interplay of Hydrogen Abstraction and Radical Repair in the
Generation of Single- and Double-Stranded DNA Damage by the
Esperamicins. J. Epstein, X. Zhang, G. Doss, J. Liesch, B. Krishnan, J.
Stubbe and J. Kozarich; J. Am. Chem. Soc. 1997, 119, 6731-6738.\
2. Himastatin: A new antitumor antibiotic from Streptomyces
Hygroscopicus . III. Structure Elucidation. J. Leet, D.Schroeder, J.
Golik, J. Matson, T. Doyle, K. Lam, S. Hill, M. Lee, J. Whitney and
B.Krishnan; J. Antibiotics 1996, 49, 299-311.\
3. Biochemical Mechanism of the E. coli Glutamate Racemase and Its
Activation by UDP-N-acetylmuramyl-L-alanine. H. Ho, P. Falk, K. Ervin,
B. Krishnan, L. Discotto, T. Dougherty and M. Pucci; Biochemistry 1995,
34, 2464-2470.\
4. Fluorescence Polarization Studies of the Binding of BMS 181176 to
DNA. B. Krishnan, M. Moore, C.LaVoie, B. Long, R. Dalterio, H. Wong and
I.E. Rosenberg; J.Biomolecular Structure & Dynamics 1994, 12(3),
625-636.\
5. E.E. Blatter, J.F. Vollano, B.S. Krishnan and J.C. Dabrowiak,
\"Interaction of the antitumor agents cis,cis,trans-Pt(IV) (NH3)2Cl2 and
cis,cis,trans-Pt(IV)-\[(CH3)2CHNH2\]2Cl2(OH)2 and their reduction
products with PM2 DNA\", Biochem., 23, 4817-4820 (1984).\
6. E.E. Blatter, J.F. Vollano, B.S. Krishnan and J.C. Dabrowiak,
\"Platinum (IV) antitumor agents\", in \"Molecular Basis of Cancer\",
Part B: Macromolecular Recognition, Chemotherapy, and Immunology, p.
185-191 (1985).

**Joseph W. Lam, PhD, Research Officer, Institute of National
Measurement Standards, National Research Council of Canada.** Part of
our group\'s mandate is produce environmental certified reference
materials. My main research is to determine trace metals by ICP-MS to
support our group activity. My main research interest areas are: sample
introduction technique, interference reduction, mixed-gas ICP.

1\. Determination of As and Se in Seawater by Flow Injection Vapor
Generation ETV-ICP-MS. At. Spec.,1999, 20, p79.

2\. The IRMM International Measurement Evaluation Programme (IMEP)
IMEP-7: Inorganic Components in human serum. Accred Qual. Assur., 1999,
4, 463.\
3. Reduction of metal oxides by carbon in graphite furnaces. Part 1, J.
Anal. At. Spectrom., 1999, 14, 1019.

**Hong In Lee, PhD, Research Fellow, Laboratory of Biochemistry, NHLBI,
NIH.** Ph.D. (1994) Michigan State University. Interested in
charaterizing metal sites, metal-substrate, and metal-inhibitor
interactions in metalloenzymes by using EPR, ESEEM, and ENDOR
spectroscopies.

Recent Publications:

1\. Hong-In Lee, Morten Sørlie, Jason Christiansen, Rutian Song, Dennis
R. Dean, Brian J. Hales, and Brian M. Hoffman, &#8220;Characterization
of an Intermediate in the Reduction of Acetylene by the Nitrogenase
a-Gln195 MoFe protein by Q-band EPR and 13C, 1H ENDOR&#8221;, J. Am.
Chem. Soc., Accepted for publication.;

2\. Joshua Telser, Hong-In Lee, and Brian M. Hoffman,
&#8220;Investigation of Exchange Couplings in \[Fe3S4\] + by Electron
Spin-Lattice Relaxation&#8221;, J. Bio. Inorg. Chem., Accepted for
publication.;

3\. Matthew J. Ryle, Hong-In Lee, Lance C. Seefeldt, Brian M. Hoffman,
\" Nitrogenase Reduction of Carbon Disulfide: Freeze-Quench EPR and
ENDOR Evidence for Three Sequential Intermediates with Cluster-Bound
Carbon \", Biochemistry, 39, 1114-1119 (2000).

**Peter Leopold, PhD, Vice President, ProteiGene Inc..** ProteiGene
develops applications of mass spectrometry in the health sciences and
agriculture.

**Cathy W. Levenson, PhD, Associate Professor, Program in Neuroscience,
Florida State University.**

Interests: Metal regulation of gene expression; Metal regulation of
cellular integrity and repair mechanisms: Role of zinc & gene expression
after brain injury, Role of copper and copper-responsive genes in
hepatic death, Role of zinc and copper in neuronal apoptosis and
necrosis; Gene expression and trace metals (Cu, Zn, Fe) during cellular
differentiation and development.

Recent Publications:\
1. Fitch, C.A., Song, Y., and Levenson, C.W. Developmental regulation of
hepatic ceruloplasmin mRNA and serum activity by exogenous thyroxine and
dexamethasone. Proc. Soc. Exp. Biol. Med. 221, 27-31,1999.\
2. Yeiser, E.C., Lerant, A.A., Casto, R.M. and C.W. Levenson. Free zinc
increases at the site of injury after cortical stab wounds in mature but
not immature rat brain. Neurosci. Lett. 277:75-78, 1999.\
3. Yeiser, E.C., Fitch, C.A., Horning, M.S. and Levenson, C.W.
Regulation of metallothionein-3 mRNA by thyroid hormone in developing
rat brain and primary cultures of rat astrocytes. Brain Res. Develop.
Brain Research 115, 195-200, 1999.\
4. Levenson, C.W., Song, Y., Narayanan, V.S., Fitch, C.A., and Yeiser,
E.C. Regulation of mitochondrial cytochrome b mRNA by copper in cultured
human hepatoma cells (Hep G2) and rat liver. Biol. Trace Element Res.
70, 1-16, 1999.\
5. Rutkoski, N.J., Fitch, C.A., Yeiser, E.C., Dodge, J., Trombley, P.Q.,
and Levenson, C.W. Regulation of neuropeptide Y mRNA and peptide
concentrations by copper in rat olfactory bulb. Brain Res. Molec. Brain
Res. 65, 80-86, 1999.\
6. Fitch, C.A., Song, Y., and Levenson, C.W. Developmental regulation of
hepatic ceruloplasmin mRNA and serum activity by exogenous thyroxine and
dexamethasone. Proc. Soc. Exp. Biol. Med. 221, 27-31,1999.\
7. Badisa, R.B. Chaudhuri, S.K. Pilarinou, E. Rutkoski, N.J. and
Levenson, C.W. Licania michauxii Prance induces hsp 70 mRNA, inhibits
proliferation and initiates necrotic cell death in cultured HepG2 and
Caco-2 cells. Cancer Lett. 149:61-68, 2000.\
8. Levenson, C.W. and Fitch, C.A. Effect of altered thyroid hormone
status on rat brain ferritin H and ferritin L mRNA during postnatal
development. Brain Res. Develop. Brain Research 119:105-199, 2000.

**Rod Levine, MD, PhD, Section Chief, Laboratory of Biochemistry, NIH,
NHLBI.** My research focusses on the oxidative modification of proteins,
especially those which are metal catalyzed.

**Jason S. Lewis, PhD, Research Associate, Radiological Sciences,
Washington University School of Medicine.** Education: University of
Essex, B.Sc.1992, Chemistry by Dissertation, University of Kent at
Canterbury, Ph.D.1996, Biochemistry \[BBSRC Case Award with the
Institute of Cancer Research, Royal Marsden Hospital, UK (1993-1996)\].
Professional Experience: 1996-Present, Research Associate, Washington
University School of Medicine, Division of Radiological Sciences, St.
Louis, Missouri. Research Activities : The major focus of our current
research is in the design, biological evaluation and clinical
application of radiopharmaceuticals containing metal radionuclides. Two
main areas of interest currently involve the use of these isotopes for
both the diagnosis of hypoxia and the evaluation of radiolabeled analogs
of somatostatin for PET imaging and therapy.\
Selected Publications:\
1. Blower PJ, Lewis JS, Zweit J. Copper Radionuclides and
Radiopharmaceuticals in Nuclear Medicine. Nuclear Medicine and Biology
957-980, 1996.\
2. Dearling JLJ, Lewis JS, McCarthy DW, Welch MJ, Blower PJ.
Redox-active metal complexes for imaging hypoxic tissues:
structure-activity relationships in copper(II) bis(thiosemicarbazone)
complexes. Chemical Communications 22:2531-2533, 1998\
3. Lewis JS, McCarthy DW, McCarthy TJ, Fujibayashi Y, Welch MJ.
Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model.
Journal of Nuclear Medicine 40:177-183, 1999\
4. Lewis JS, Srinivasan A, Schmidt MA, Anderson CJ. In vitro and in vivo
evaluation of copper-64-TETA-tyr3-octreotate: A new somatostatin analog
with improved tissue target uptake. Nuclear Medicine and Biology
26:267-273, 1999.\
5. Lewis JS, Lewis MR, Srinivasan A, Schmidt MA, Wang J, Anderson CJ.
Comparison of four 64Cu-labeled somatostatin analogues in vitro and in a
tumor-bearing rat model: Evaluation of new derivatives for positron
emission tomography imaging and targeted radiotherapy. Journal of
Medicinal Chemistry 42:1341-1347, 1999.\
6. Lewis JS, Lewis MR, Cutler PD, Srinivasan A, Schmidt MA, Schwarz SW,
Morris MM, Miller JP, Anderson CJ Radiotherapy and Dosimetry of
64Cu-TETA-Tyr3-Octreotate in a Somatostatin Receptor-Positive
Tumor-Bearing Rat Model. Clinical Cancer Research 5:3608-3616, 1999.

**Jie Liu, PhD, MD, Scientist, Inorganic Carcinogenesis Section, NCI at
NIEHS.** I have been woking on metal toxicology during the past 10
years, and have published more than 60 papers on the role of
metallothionein in metal toxicology, and have strong interest in metals
in medicine, transporters, and therapeutic use, etc.

**Roger Luo, PhD, Visiting Research Fellow, NCI, NIH.** Chelate design
and synthesis for isotopes used in diagnosis and therapy. Radioimmune
and bioconjucate chemistry

**Linda L. McClure, Technology Information Specialist, NCI.** Have been
working on gathering information on alternative and complementary
medicine for a NCI webpage.

**Claude F. Meares, PhD, Professor, Chemistry, University of
California.** Research Interests: Bioconjugate chemistry, molecular
biology, application of chemical techniques to biological and biomedical
problems, mapping protein-protein and protein-nucleic acid interactions,
bifunctional chelating agents, monoclonal antibodies.\
188. Peterson, James J.; Meares, Claude F. Enzymatic Cleavage of
Peptide-Linked Radiolabels from Immunoconjugates. Bioconjugate
Chemistry; 10, 553-557 (1999).\
189. Goodwin, DA, Meares, CF. Pretargeted peptide imaging and therapy.
Cancer Biotherapy And Radiopharmaceuticals, 14, 145-152 (1999).\
190. Colland, F, Fujita, N, Kotlarz, D, Bown, JA, Meares, CF, Ishihama,
A, Kolb, A. Positioning of sigma(S), the stationary phase sigma factor,
in Escherichia coli RNA polymerase-promoter open complexes. EMBO
Journal, 18, 4049-4059 (1999).\
191. Miyake, R, Owens, JT, Xu, DD, Jackson, WM, Meares, CF.
Site-directed photocleavage for mapping protein architecture. Journal Of
The American Chemical Society, 121, 7453-7454 (1999).\
192. Traviglia, SL; Datwyler, SA; Yan, D; Ishihama, A; Meares, CF.
Targeted Protein Footprinting: Where Different Transcription Factors
Bind to RNA Polymerase. Biochemistry, 38, 15774-15778 (1999).\
193. Rose, LM; Deng, CT; Scott, SL; Xiong, CY; Lamborn, KR, Gumerlock,
PH; DeNardo, GL; Meares, CF. Critical Lym-1 binding residues on
polymorphic HLA-DR molecules. Molecular Immunology, 36, 789-797 (1999).\
194. Mirick, GR, O\'Donnell, RT, DeNardo, SJ, Shen, S, Meares, CF,
DeNardo, GL. Transfer of copper from a chelated Cu-67-antibody conjugate
to ceruloplasmin in lymphoma patients. Nuclear Medicine and Biology, 26,
841-845 (1999).

**Yuji Mikata, PhD, Postdoctoral Fellow, Chemistry, MIT.** Permanent
Address: Department of Chemistry, Nara Women\'s University, Nara
630-8506, Japan. Biography: 1988-1993 PhD., Kyoto University, Japan,
Advisor:Prof. A. Ohno; 1993-present Research Associate, Nara Women\'s
University, Japan, Advisor: Prof. S. Yano; 1999-present Japan Society of
Promotion of Science (JSPS) Postdoctral Fellow, Advisor Prof. S. J.
Lippard, MIT. Research interests: Developing of new platinum drugs
(Inorg. Chim. Acta, 279, 51, 1998); photodynamic therapy by sugar-bound
porphyrins (Tetrahedron Lett., 39, 4505, 1998); deazaflavin derivatives
as new bioreductive drugs (Bioorg. Med. Chem. Lett., 9, 2141, 1999);
investigation of sugar-metal interactions (Chem. Lett., 255, 1999)

**Nancy J. Miller-Ihli, PhD, Research Chemist, Food Composition Lab,
USDA.** I am an analytical chemist working in trace element research
using atomic spectroscopic tools. I have experience with AAS, ICP-AES
and ICP-MS. Our laboratory has experience with a wide range of
biological and botanical sample types and sample preparation strategies.
We work at trace and ultratrace levels and more recently are making
speciation measurements for elements such as cobalt and arsenic. A list
of publications is available upon request.

**John A. Milner, PhD, Acting Chief, Division Cancer Prevention, NCI,
Nutritional Science Research Group.** On leave from Penn State
University where I have served as Head of the Nutrition Department for
the past 10 years. Current research interest are in how selected
components of the diet influence cancer risk. During almost 25 years in
academia I have devoted efforts to how selenium can alter the cancer
process. More recently my focus has been on how allyl sulfur compounds
alter molecular targets involved in carcinogen bioactivation and tumor
proliferation.

**Janet R. Morrow, PhD, Associate Professor of Chemistry and Medicinal
Chemistry, Chemistry, State University of New York at Buffalo.** B.S.
Chemistry, 1980, University of California, Santa Barbara, Ph.D.
Chemistry, 1985, University of North Carolina, Chapel Hill, N.S.F.
Postdoctoral Fellow, 1985-1986, University of Bordeaux, Postdoctoral
Fellow, 1986-1988, University of California, San Diego, Assistant
Professor 1988-1994, SUNY, Buffalo; Associate Professor 1994-present,
SUNY, Buffalo; Research interests: Synthetic nucleases for RNA and DNA
cleavage, metal complex-oligonucleotide conjugates, lanthanide and
actinide chemistry, RNA recognition.

Key publications:

1\. B. F. Baker, H. Khalili, N. Wei, J.R. Morrow, \"Cleavage of the
5\'-Cap Structure of m-RNA by an Europium(III) Macrocyclic Complex with
Pendant Alcohol Groups\" J. Am.Chem. Soc. 1997, 119, 8749-8755.

2\. L.L. Chappell, D.A.Voss, Jr., W. DeW. Horrocks, Jr.; J.R. Morrow,
\"The Effect of Mixed Pendent Groups on the Solution and Catalytic
Properties of Eu(III) Macrocyclic Complexes: Bifunctional and
Monofunctional Amide and Alcohol Pendants in Septadentate and
Octadentate Ligands\" Inorganic Chemistry 1998, 37, 3989-3998.

3\. B.F. Baker, S.S. Lot, J. Kringel, S. Cheng-Flournoy, P. Villiet,
H.M. Sasmor, L.L. Chappell, J.R. Morrow, \"Oligonucleotide-Europium
Complex Conjugate Designed to Cleave the 5\'-Cap Structure of the ICAM-1
Transcript Potentiates Antisense Activity in Cells\" Nucleic Acids
Research 1999, 27, 1547-1551. 4. K.P. McCue, J.R. Morrow, \"Hydrolysis
of a 5-Cap Model for mRNA by Dinuclear Cu(II) and Zn(II) Complexes.
Rapid Hydrolysis by Four Metal Ions\" Inorganic Chemistry 1999, 38,
6136-6142.

5\. L. Huang, L.L. Chappell, B.F. Baker, J.R. Morrow, J.
R.\"Oligonucleotide Conjugates of Eu(III) Tetraazamacrocycles with
Pendent Alcohol and Amide groups Promote Sequence-Specific Cleavage oF
RNA\" J. Biol. Inorg. Chem. 2000, 5(1) 85-92.

6\. D.M. Epstein, L.L. Chappell, H. Khalili, R.M. Supkowski, W.DeW.
Horrocks, Jr.; J.R. Morrow \"Eu(III) Macrocyclic Complexes Promote
Cleavage of and Bind to Models for the 5\'-Cap of mRNA. Effect of
Pendent Group and a Second Metal Ion\" Inorganic Chemistry 2000, 39,
2130

**David B. Newlin, PhD, Research Psychologist, NIDA, NIH \--
Intramural.** I have a strong interest in medicinal uses of metals,
particulary gold and platinum.

**Ronald E. Noftle, PhD, Professor of Chemistry, Chemistry, Wake Forest
University.** Ph.D. University of Washington, 1966; B.S.University of
New Hampshire, 1961; Post-doctoral Fellow, University of Idaho, 1966-67;
Visiting Professor: U. S. Naval Research Laboratory, 1975-76; Visiting
Professor:University of Southampton, 1987, 1989, 1995; Interests:
Synthetic main group chemistry, vibrational spectroscopy. New Interests:
electrochemistry of thiophene species, metal complexes of biochemical
interest, mechanism of oxidation of toxins.\
Recent papers:\
1. Investigation of the Lifetimes of Some Pyrrole Species by Rapid Scan
Cyclic Voltammetry and Double Potential Step Techniques, Narula, P. M;
Noftle, R. E. J. Electroanal. Chem., 1999, 464, 123-127.\
2. Synthesis and Characterization of Thiophenes With Fluorinated
Substituents, Ritter, S.. K.; Hill, B. K.; Odian, M. A.; Dai, J.;
Noftle, R. E.; Gard, G. L. J. Fluorine Chem., 1999, 93, 73-79.\
3. Characterization and Crystal Structures of Some Fluorinated Imides,
Narula, P. M.; Day, C. S.; Odian, M. A.; Pennington, W. T.; Lachgar, A.;
Noftle, R. E. Polyhedron, 1999, 18, 1751-1759.\
4. Cleavage of Substituents Upon Oxidative Polymerization of Substituted
Thiophenes, Ritter, S. K.; Noftle, R.E. Inorg. Chim. Acta, 1999, 287,
232-237.

**Robert W. Odom, PhD, Senior Scientist and Manager, Analytical
Contracts, Charles Evans & Associates.** Dr. Robert W. Odom has had
extensive experience in the study of ion formation mechanisms and
ion-molecule reactions and has designed and developed novel ion sources
and mass spectrometry instrumentation. Dr. Odom has been involved in a
number research activities over the past 18 years with Charles Evans &
Associates including development of analytical methods for metals
analysis in nanovolumes, development of secondary ion mass spectrometry
(SIMS) imaging techniques for elemental and molecular imaging of
biomaterials the use of pattern recognition techniques to classify
complex data. His research interests also include developing innovative
techniques for the analysis of biomolecules including molecular ion
imaging mass spectrometry and development of new methods of matrix
assisted laser desorption ionization (MALDI).\
1. \'Quantitative Trace Element Analysis of Microdroplet Residues by
Secondary\
Ion Mass Spectrometry,\' R. W. Odom, G. Lux, R. H. Fleming, P. K. Chu,
I. C.\
Niemeyer and R. J. Blattner, Anal. Chem., 60, 2070 (1988).\
2. \'Quantification of Boron in Biological Tissue by Secondary Ion Mass\
Spectrometry\', V.K.F. Chia, R.J. Bleiler, D.B. Sams, C.M. Jones, R.W.
Odom,\
W.F. Bauer, A.K. Gianotto and J.P. Weidner in Advances in Neutron
Capture\
Therapy, Ed. A.H. Soloway et. al, Plenum Press, New York, 1993\
3. \'Secondary Ion Mass Spectrometry Ion Imaging in Microscopic and\
Spectroscopic Imaging of the Chemical State, Ed. M.D. Morris, Plenum
Press,\
New York, 1993. and published in Appl. Spectros. Rev., 29, 67 (1994).\
4. \'XPS and ToF-SIMS Microanalysis of a Peptide/Polymer Drug Delivery
Device\',\
C.M.John, R.W. Odom, L. Salvati, A. Annapragada and M.Y. Fu Lu,
Anal.Chem.,\
67, 3871(1995).

**Alan B. Packard, MD, Sr. Research Associate/Asst. Professor, Nuclear
Medicine, Children\'s Hospital/Harvard Medical School.** Affiliations:
Children\'s Hospital/Harvard Medical School. Research Interests: Our
laboratory is currently engaged in the development of transition-metal
based radiopharmaceuticals for cancer imaging and therapy. The focus of
the imaging program is on the development of Cu-64-based PET agents that
can be used to non-invasively evaluate the multidrug resistance status
of patients with breast and other types of cancer. These new copper
complexes are, like MDR chemotherapeutics, substrates for Pgp, the
protein implicated in MDR1 multidrug resistance.\
Citations:

1\. Packard AB, Day PJ, Kronauge JF, Treves ST. Synthesis and
biodistribution of 64Cu-labeled Monocationic Diiminedioxime Copper(II)
Complexes. Nucl Med Biol, 25;531-537 (1998)\
2. Packard AB, Day PJ, Kronauge JF, Wen P, Treves ST. Lipophilic
cationic copper complexes as PET radiopharmaceuticals. J Labelled Compd
Radiopharm, 40;484-486 (1997)

**Sanjay K. Pandey, PhD, Visiting Fellow, Diabetes Section, NIH/NIA.** I
have been working in the area of insulin signaling. My PhD thesis
project was to explore the mechanism by which trace metal ion Vanadium
exert its insulinomimetic effects. Presently i am working on apoptosis
and using vanadium as a toolto find whether it also modulate apoptoic
phenomenon similar to insulin. My publications:

1\. Pandey S.K. et al. Biochemistry, 1999, 38,14667-75.\
2. Pandey S.K et al. Biochemistry, 1998, 37, 7006-14.

**Irina V. Panyutin, MD, Staff scientist, NMD, NIH/CC.** DNA target with
various radioisotops linked to oligonucleotides to produce gene damage.

**Dierdre A. Pearce, PhD, Postdoctoral, Department of Chemistry,
Massachusetts Institute of Technology.** PhD ANU Canberra, Australia
(bioinorganic chemistry). Post doc 97-present with Professor Barbara
Imperiali (now at MIT). Research interests includes the development of
novel fluorescent peptidyl-chemosensors for transition metal ions.
(Pearce, DA, Walkup, GK and Imperiali, B, Biorg. Med. Chem. Lett., 8,
1998, 1963. Most recently, involved with the preparation of
hydroxyquinoline derivatives and incorporation of these derivatives into
peptidyl-chemosensors for detection of Zn(II) in pseudo-biological
conditions.

**Michael L. Pendrak, PhD, CRTA, Laboratory of Pathology, NCI.** General
Research Interest: Heme catabolism by microorganisms.

**David H. Petering, PhD, Professor of Chemistry, Chemistry, University
of Wisconsin-Milwaukee.**

David Petering is Professor of Chemistry at the University of
Wisconsin-Milwaukee and Director of the National Institute of
Environmental Health Sciences Marine and Freshwater Biomedical Sciences
Center at the university. Petering\'s research integrates projects in
biologically essential transition metal metabolism, metal toxicology and
mechanism of action of metallodrug from the inorganic biochemical and
cellular perspectives. He has published extensively in the area of
metallodrugs, including inorganic, biochemical and cellular studies on
the antitumor agents bleomycin, cis-platin, adriamycin, mono- and
bis-thiosemicarbazonato Cu complexes as well as other experimental
cytotoxic agents. He also maintains a major program of research on the
toxicology of cadmium, ranging from chemical and biochemical research on
metallothionein to work on the mechanism of inhibition of
sodium-dependent nutrient transporters in the kidney. In addition, he
has published widely on the structure and reactivity of Zn, Cu, and Cd
metallothioneins with a focus on interprotein ligand substitution
reactions related to the activation of Zn proteins and the reactivity of
the sulfhydryl groups in the protein with electrophiles and hydrogen
peroxide. These have been complemented by cellular investigations
probing the biological significance of these reactions, particularly in
tumor cells. A complementary emphasis on tumor cell zinc metabolism has
been developed which centers on the role of metallothionein in zinc
acquisition and distribution. Studies on the reductive mobilization of
iron from transferrin and the reactivity of Zn finger centers in
relation to toxic metals rounds out Petering\'s research. Petering also
directs an NIH center devoted to using aquatic model systems in
biomedical studies of toxic metals and organic compounds. A sampling of
recent papers related to some of these areas is provided below:\
1. Cadmium and lead interactions with transcription factor IIIA from
Xenopus laevis: a model for zinc finger protein reactions with toxic
metal ions and metallothionein, Mar. Environ. Res. in press.\
2. Interprotein metal ion exchange between cadmium-carbonic anhydrase
and apo-or zinc-metallothionein, J. Ejnik et al, J. Bioinorg. Chem., 4:
784-790 (1999).\
3. Characterization of the cadmium complex of peptide 49-61: a putative
nucleation center for cadmium-induced folding in rabbit liver
metallothionein IIA, Munoz et al, J. Bioinorg. Chem. 4:495-507 (1999)\
4. Cadmium decreases SGLT1 messenger RNA in mouse kidney cells,
Blumenthal et al, Toxicol. Appl Pharmacol. 149:49-54 (1998).\
5. Fe- and Co-Bleomycins bound to site specific and nospecific DNA
decamers: comparative binding and reactivity of their metal centers,
Fulmer et al, Biochemistry 36: 4367-4374.\
6. Metallobleomycin-DNA interactions: structures and reactions related
to bleomycin-induced DNA damage, Petering et al, Metal Ions in
Biological Systems 33:619-648 (1996)

**Abbas Pezeshk, PhD, Professor and Chair, Chemistry, Moorhead State
University.**

Member: American Chemical Society; Physical Chemistry/Biophysics;
Inorganic Chemistry ; Red River Valley Section of ACS; Minnesota Academy
of Science. RESEARCH INTERESTS: In brief, I am interested in the
following areas: 1. Synthesis of potentially active antitumor antibiotic
drugs, 2. Studies of metalloenzymes, such as cytochrome c oxidase, and
nitrous oxide reductase, 3. The effects of radiation on DNA, studies of
the primary and the secondary radicals, 4. The effects of antioxidants
on blood pressure and membrane fluidity in hypertensive and normotensive
rats, 5. Membrane permeability of antitumor drugs and
metallo-porphyrins, and 6. Magnetic resonance spectroscopy of biological
compounds such as coenzyme B12.

**Mary Frances A. Picciano, Visiting Nutritionist, NIH, Office of
Dietary Supplements.** I am normally a Professor of Nutrition at the
Pennsylvania State University with a long-standing research interest in
maternal, infant and child nutrition. In this capacity, I have
investegated several minerals from a nutritional perspective. My most
recent interests that center around minerals dealth with selenium and
iron. Representative publications follow:

1\. Picciano, M.F. Mineral Nutrition During Lactation. In: Clinical
Nutrition of the Essential Trace Elements and Minerals- The Guide for
Health Professionals, edited by Bendich, A., Bogden J. D., and Klevay L.
Totowa, N.J: Humana Press, Inc. Chapter 12, (in press).

2\. Moriarty, P., M.F. Picciano, J. Beard and C.C. Reddy. Classical
selenium-dependent glutathione peroxidase expression is decreased
secondary to iron deficiency in rats. J. Nutr. 125:293-301, 1995.

3\. McGuire, M.K., S.L. Burgert, J.A. Milner, L. Glass, R. Kummer, R.
Deering, R. Boucek and M.F. Picciano. Selenium status of infants is
influenced by supplementation of formula or maternal diets. Am. J. Clin.
Nutr. 58:643-48, 1993.

**Patricia A. Pleban, PhD, Associate Professor, Dept. Chemistry &
Biochemistry, Old Dominion University.** I am currently an associate
professor in the Department of Chemistry & Biochemistry at Old Dominion
University. I am a clinical chemist by training and also run a small
specialty lab, the Old Dominion Univeristy Trace Element Laboratory. My
interest in human trace element metabolism and analysis has spanned more
than 20 years. Currently we are developing NMR techniques to look at
selenium-containing biomolecules. The large NMR chemical shift range for
selenium compounds (2000 ppm)provides a sensitive probe of the chemical
environment around the selenium atom. Ultimately, this research is aimed
at probing the chemical forms selenium as it functions as an
antioxidant. Other research has involved alterations in trace metal
metabolism during growth hormone deficiency and therapy (emphasis on
selenium and zinc), trace metal metabolism during diabetic ketoacidosis
and its resolution, speciation of selenium in human blood. Past
publications include:

1\. \"Trace Element Metabolism in the Foetus & Neonate\". PA Pleban, B
Numerof, F Wirth. Clinics Endocrinol. Metabol. 14:545-566 (1985);

2\. \"The Effect of Lactose Administration on Mineral Absorption in
Small, Premature Neonates\". Wirth FH, Numerof B, Pleban P, Neylan MJ.
J. Pediat. 114:283-287 (1990),

3\. \"Magnesium, Zinc and Copper Levels in Plasma and Blood Cellular
Components in Children with IDDM\". Rohn R, Jenkins L, Pleban P. Clin.
Chim. Acta 215:21-28 (1993).

**Peter C. Preusch, PhD, Program Director, Pharmacology, Physiology, and
Biological Chemistry, National Institute of General Medical Sciences.**
Program Director, PPBC Division, NIGMS, NIH, 1992-present. Responsible
for research grant portfolios in bioinorganic chemistry and
metallobiochemistry, bioenergetics and redox enzymology, also
responsible for pharmacological sciences training grants. Previously SRA
with Special Review Section, DRG, NIH, 1990-1992.

**Steven Yue Qian, PhD, Visiting Fellow, , LPC/NIEHS/NIH.** Ph.D. in
Free Radical and Radiation Biology. Visiting Fellow, Laboratory of
Pharmacology and Chemistry, National Institute of Environmental Health
Sciences, National Institutes of Health (NIEHS/NIH), Research Triangle
Park, North Carolina, USA. Research Interests: Free radical chemistry as
related to health problems. Iron in disease: iron catalysis of free
radical reaction in lipid peroxidation. Protein-derived and
membrane-derived radicals in human diseases. Current Projects: Study of
free radical metabolites of toxic chemicals, drugs, and biochemical
consequences via ESR, HPLC, and MS.

**Stephen W. Ragsdale, PhD, Professor, Biochemistry, University of
Nebraska.** B.S. Chemistry & Biochemistry, 1979, Univ. of Georgia,
Athens, GA; Ph.D. Biochemistry, 1983, Univ. of Georgia, Athens, GA, Lars
G. Ljungdahl, mentor; Postdoctor, 1984-87, Case Western Reserve Univ.,
Cleveland, OH. Harland G. Wood, mentor; Asst Professor, Dept of
Chemistry, Univ. of Wisconsin- Milwaukee 1987-1991; Assoc Professor,
Dept of Biochemistry, Univ. of Nebraska- Lincoln 1991 -1996; Professor,
Dept of Biochemistry, Univ. of Nebraska, Lincoln, Nebraska 1996-present.
CURRENT PROFESSIONAL ACTIVITIES: EDITORIAL BOARDS: Journal of Biological
Chemistry, Journal of Bacteriology, BioFactors Archives of Biochemistry
and Biophysics. LEADERSHIP IN PROFESSIONAL SOCIETIES: Chair-elect (1999)
and Chair (2000), Div. K of Am. Soc. for Microbiology; Nominations
Committee, Div. K of Am. Soc. for Microbiology (2000); Treasurer, Biol.
Chem. Div. of Am. Chem. Society, 1999-2002.\
PUBLICATIONS: (yr 2000, 90 total):

1\. Ragsdale, S.W. (2000) Ni containing CO dehydrogenase and
hydrogenase, in \"Enzyme catalysed electron/radical transfer\" Nigel
Scrutton, Editor.

2\. Ragsdale, S.W. and Thauer, R. (2000) One-carbon chemistry: CO2, CO,
CH4, formate: 1. Reductive chemistry. In Valentine, Bertini, and Gray
(ed.), Biological Inorganic Chemistry: Structure and Reactivity.
University Science Books. In press.

3\. Seravalli, J., and Ragsdale, S.W. (2000) Channeling of Carbon
Monoxide During Anaerobic Carbon Dioxide Fixation Biochemistry: 39,
1274-1277.

4\. Telser, J., Horng, Y.-C., Becker, D., Hoffman, B., and Ragsdale,
S.W. (2000) On the assignment of nickel oxidation states of the Ox1 and
Ox2 Forms of Methyl-Coenzyme M Reductase. J. Am. Chem. Soc., 122:
182-183.

5\. Murakami, E., and Ragsdale, S.W. (2000) Evidence for Intersubunit
Communication During Acetyl-CoA Cleavage by the Multienzyme CO
Dehydrogenase/Acetyl-CoA Synthase Complex from Methanosarcina
thermophila: Evidence that the Beta Subunit Catalyzes C-C and C-S Bond
Cleavage. J. of Biol. Chem. 275: 4699-4707.

**Daniel J. Raiten, PhD, Health Scientist Administrator, Office of
Prevention Research and Interntl Prog., NIH/NICHD.** Research interest:
maternal and child health, nutrition, international health with emphasis
on resource-poor countries.

**Martina Ralle, PhD, Research Scientist, BMB, Oregon Graduate Institute
of Science and Technolog.** 8/96-present, Research Scientist (until
6/99: Senior Research Associate) with Prof. Dr. N. J. Blackburn,
Department of Biochemistry and Molecular Biology, Oregon Graduate
Institute of Science and Technology; 10/94-7/96, Postdoctoral Research
Associate with Prof. Dr. B. Wunderlich, University of Tennessee and Oak
Ridge National Laboratory; 10/93-06/95, Postdoctoral Research Associate
with Prof. Dr. C. E. Barnes, University of Tennessee; 1993 Ph.D.,
Solid-state Chemistry, Prof. Dr. M. Jansen, University of Bonn, Germant.
Affiliations: Member of the American Chemical Society Research
Interests: Metal in Biology, esp. metal transport in mammalian cells,
focussing on Fe and Cu. Determination of the metal binding/transport
sites and mechanism through X-ray absorption.

Recent Publications:\
1. N. J. Blackburn, M. Ralle, R. Hassett, and D. J. Kosman.
Spectroscopic Analysis of the Trinuclear Cluster in the Fet3 Protein
from Yeast, a Multinuclear Copper Oxidase, Biochemistry 39, (2000)
2316-2324.\
2. M. Ralle, M. J. Cooper, S. Lutsenko, N. J. Blackburn; \"The Menkes
Disease Protein Binds Copper via Novel 2-Coordinate Cu(I)-Cysteinates in
the N-Terminal Domain\"; Journal of the American Chemical Society
120(51); 13525-13526 (1998)

**Charles G. Riordan, PhD, Research Scientist, Chemistry and
Biochemistry, University of Delaware.** B.A. Chemistry, 1986, College of
the Holy Cross, Worcester, MA; Ph.D. Chemistry, 1990, Texas A&M
University with Marcetta Darensbourg; Postdoctoral Fellow, 1990-92,
University of Chicago with Jack Halpern; Assistant Professor, 1993-97,
Kansas State University; 1997, Associate Professor, Kansas State
University; Associate Professor, University of Delaware, 1997-present;
Assistant Chair, Department of Chemistry and Biochemistry, University of
Delaware, 1999-present. 1994-99 NSF Young Investigator; 2000 Editorial
Board, Inorganic Chemistry. Research Interests: Coordination and
organometallic chemistry, ligand design, design of organometallic
complexes for photodynamic therapy, bioorganometallic chemistry of
nickel and zinc.

Representative Publications:\
1. Pyrazolyl((methylthio)methyl)borates: Hybrid Ligands with Nitrogen
and Sulfur Donors Chem. Commun. 1999, 159-160.\
2. Phenyltris((tert-butylthio)methyl)borate: A Second Generation S3-
Ligand that Enforces Tetrahedral Coordination\" Inorg. Chem. 1998, 37,
4754-4755.\
3. Kinetics and Mechanism of Alkyl Transfer from Organocobalt(III) to
Nickel(I): Implications for the Synthesis of Acetyl Coenzyme A by CO
Dehydrogenase J. Am. Chem. Soc. 1997, 119, 1648-1655.\
4. The Role Of Nickel In Acetyl-CoA Synthesis By The Bifunctional Enzyme
CO Dehydrogenase/Acetyl-CoA Synthase: Enzymology And Model Chemistry J.
Biol. Inorg. Chem. 1996, 1, 489-493.\
5. Methyl Radical Initiated DNA Cleavage Facilitated by a Discrete
Organometallic Complex J. Am. Chem. Soc. 1994, 116, 2189-2190. Y
Associate Professor

**Kenton R. Rodgers, PhD, Associate Professor, Chemistry, North Dakota
State University.**

B.S., 1981; M.A., 1982, in chemistry, University of Missouri; Ph.D.,
1988, in inorganic chemistry, University of Iowa. Postdoctoral fellow,
1989-1993, Princeton University; Asst. Prof., 1993-1998, Assoc. Prof.,
1998-present, North Dakota State Univ.; Presidential Early Career Award
for Scientists and Engineers, 1996. Research Interests: My interests
center around spectroscopic studies of metalloproteins and enzymes,
particularly heme proteins. We use primarily resonance Raman,
time-resolved absorbance, ESR and NMR to probe the metal sites in these
proteins. Our major efforts are currently directed toward the study of
two heme proteins. KatG: This is a heme catalase-peroxidase enzyme found
in Mycobacterium tuberculosis. Current evidence indicates that KatG
activates isoniazid (INH), one of the most widely used antitubercular
drugs, toward inhibition of mycolic acid synthesis. Point mutations in
the vicinity of the heme of this enzyme are highly correlated with
resistance of M. tuberculosis to INH. By using spectroscopic probes of
the prosthetic heme, we are currently working to understand (a) the
effects of mutation on the structure and chemistry of the heme and (b)
mutation- induced changes in the interactions between KatG and INH.
FixL: FixL is a heme-based oxygen-sensing protein and is the sensor
component of a bacterial two-component system responsible for regulating
gene transcription in the cascade leading to nitrogen fixation in
Rhizobium meliloti. This membrane-bound protein contains heme and kinase
domains. The kinase activity is regulated by the spin state of the heme,
which is switched between high spin and low spin forms by reversible
binding of oxygen. We are using spectroscopic probes of the heme to
build an understanding of the coupling of interchange between heme
states to regulation of kinase activity.

Selected Publications\
1)Lukat-Rodgers, G. S.; Wengenack, N. L.; Rusnak, F.; Rodgers, K. R.
\'Spectroscopic Comparison of the Heme Active Sites in WT KatG and its
S315T Mutant\' submitted to Biochemistry.\
2)Lukat-Rodgers, G. S.; Tang, L.; Rodgers, K. R. \'Spectroscopic Studies
of Ntrosyl FixL: Probing the Oxygen Receptor Site that Regulates
Nitrogen Fixation\' submitted to Journal of Biological Inorganic
Chemistry.\
3)Holland, P. L.; Wilkinson, E. C.; Mahapatra, S.; Rodgers, K. R.; Que,
L.; Tolman, W. B. \'Resonance Raman Studies on the Bis(µ-oxo)dicopper
Core\' J. Am. Chem. Soc in press.\
4)Rodgers, K. R.; Lukat-Rodgers, G. S.; Tang, L. \'Spectroscopic
observation of a FixL switching intermediate\' J. Am. Chem. Soc. 1999,
121, 11241-11242.\
5)Rodgers, K. R. \'Heme-based Sensors in Biological Systems\' Current
Opinion in Chemical Biology 1999, 3, 158-167.\
6)Hu, X; Rodgers, K. R.; Mukerji, I.; Spiro, T. G. \'New Light on
Allostery: Dynamic Resonance Raman Spectroscopy of Hemoglobin Kempsey\'
Biochemistry 1999, 38, 3462-3467.\
7)Holland, P. L.; Rodgers, K. R.; Tolamn, W. B. \'Is the
Bis(µ-oxo)dicopper Core Capable of Hydroxylating an Arene?\' Angew.
Chem. Int. Ed. Engl. 1999, 38, 1139-1142.\
8)Mokhir, A. A.; Rodgers, K. R. \'Synthesis and Characterization of
Homo- and Heterometallic meso- pyridylporphyrin Dimers\' in preparation
for Inorg.Chem. 9)Gerasimchuk, N. N.; Mokhir, A. A.; Rodgers, K. R.
\'Synthesis and Characterization of Dimeric Mutually- coordinated
Magnesium meso-2-pyridylporphyrins\' Inorg. Chem. 1998, 37, 5641-5650.\
10)Lukat-Rodgers, G. S.; Rexine, J. L.; Rodgers, K. R. \'Heme Speciation
in Alkaline Ferric FixL and Possible Tyrosine Involvement in the Signal
Transduction Pathway for Regulation of Nitrogen Fixation\' Biochemistry,
1998, 37, 13543-13552.\
11)Lukat-Rodgers, G. S.; Rodgers, K. R. \'Spin-state Equilibria and
Axial Ligand Bonding in FixL Hydroxide: A Resonance Raman Study\' J.
Biol. Inorg. Chem. 1998, 3, 274-281.\
12)Lukat-Rodgers, G. S.; Rodgers, K. R. \'Characterization of Ferrous
FixL Nitric Oxide Adducts by Resonance Raman Spectroscopy\' Biochemistry
1997, 36, 4178-4187.\
13)Rodgers, K. R.; Lukat-Rodgers, G. S; Barron, J. A. \'The Structural
Basis for Ligand Discrimination and Response Initiation in the
Heme-Based Oxygen Sensor, FixL,\' Biochemistry 1996, 35, 9539-9548.

**Michael E. Rogers, PhD, Division Director, PPBC, NIGMS.** I serve as
director of the Pharmacology, Physiology, and Biological Chemistry
Division, NIGMS,responsible for the planning, organization, and
administration of a large national program of grants and fellowship
awards in the pharmacological, physiological, biochemical, and chemical
sciences. I previously served as scientific review administrator for the
NIH Bio-organic and Natural Products Chemistry Study Section, and prior
to that, as Assistant Professor of Medicinal Chemistry in the School of
Pharmacy, Virginia Commonwealth University.

**Steve Rokita, PhD, Professor, Chemistry and Biochemistry, University
of Maryland.** B.S., 1979, University of California at Berkeley; Ph.D.,
1983, Massachusetts Institute of Technology; NIH Postdoctoral
Fellowship, 1984-1986, Rockefeller University. Catacosinos Young
Investigator for Cancer Research, 1988. Ad Hoc member, Bioorganic and
Natural Products Study Section, NIH, 1993; Molecular Biochemistry
Advisory Panel, NSF 1993-1996; Member, Bioorganic and Natural Products
Study Section, NIH, 1997-present; Advisory Board of Bioconjugate
Chemistry. Vice-Chair, 1998 and Chair, 1999, Bioorganic Chemistry Gordon
Conference. Area of Research. Bioorganic/biochemistry. Nucleic acid
structure and reactivity; therapeutic and toxicology aspects of DNA
modification; redox enzymology, enzyme mechanisms of dehalogenation;
biological and biomimetic reactions of nickel.

A few publications:\
1. James Muller, Lou Anne Kayser, Sari Paikoff, Victor Duarte, Ning
Tang, Ronelito Perez, Steven E. Rokita and Cynthia J. Burrows\*
\"Formation of DNA Adducts Using Nickel(II) Complexes of Redox-Active
Ligands: A comparison of salen and peptide complexes\" Coord. Chem. Rev.
1999, 186, 761-774.\
2. Ning Tang, James G. Muller, Cynthia J. Burrows and Steven E. Rokita\*
\"Nickel and Cobalt Reagents Promote Selective Oxidation of Z-DNA\"
Biochemistry 1999, 38, 16648-16654.\
3. Hui-Chen Shih, Helina Kassahun, Cynthia J. Burrows and Steven E.
Rokita\* \"Selective Association between a Macrocyclic Nickel Complex
and Extrahelical Guanine Residue\" Biochemistry 1999, 38, 15034-15042.

**Clifford S. Rossiter, Graduate Student in Medicinal Chemistry,
Department of Medicinal Chemistry, SUNY at Buffalo.** I am a graduate
student in the department of medicinal chemistry currently working on my
Ph.D. My interest are in the field of DNA cleavage and dynamic
combinatorial chemistry. I currently have two degrees; the first is in
the field of Chemical Engineering and the second is in chemistry,

**Frank M. Rusnak, PhD, Assoc. Professor, Biochemistry & Molecular
Biology, Biochemistry & Molecular Biology, Mayo Clinic and Foundation.**
Dr. Frank Rusnak received his B. S. degree in Biochemistry, 1982 from
the University of Minnesota; his Ph.D.in Biochemistry, 1988 from
University of Minnesota working on spectroscopic studies of
metalloenzymes in Professor Eckard Münck\'s laboratory. Following a
two-year NIH postdoctoral fellowship at Harvard Medical School in
Professor Christopher Walsh\'s laboratory, he moved to his current
position at Mayo Clinic. He has been Associate Professor of Biochemistry
& Molecular Biology since 1996 and is currently Section Head for
Hematology Research. Awards include Baccaner Basic Science Award, NIH
Pre- and Postdoctoral Fellowships, and a Scholarship for Invited
Scientist from À Junta Nacional de Investigação Científica e Tecnológica
Programa PRAXIS XXI/Bolsas (Portugal). He is author of nearly 50
scientific publications in bioorganic and bioinorganic chemistry,
including four book chapters and four reviews. Dr. Rusnak\'s research
interests include structure/function studies of metalloproteins and
metalloenzymes important in human health and disease. One laboratory
project includes structure/function studies of the
Ca(II)/calmodulin-dependent protein phosphatase calcineurin, an iron-
and zinc-containing metalloenzyme that is the target of anti-rejection
immunosuppressant drugs cyclosporin A and FK506. Another major project
is the role of heme-containing catalase/peroxidase from Mycobacterium
tuberculosis, KatG, in activation of the antitubercular drug isoniazid,
and the molecular basis for resistance to isoniazid afforded by point
mutations in the katG gene.

Selected publications:\
Calcineurin Structure/Function:\
1. Yu, L. et al. \'Evidence that calcineurin accommodates an active site
binuclear metal center\' (1995), JACS. 117:10147.\
2. Rusnak, F. et al. \'Metalloenzymes and signal transduction: The
protein serine/threonine phosphatases, a novel class of binuclear
metal-containing enzymes\' (1996) JBIC 1:388.\
3. Mertz, P. et al. \'Kinetic and spectroscopic analyses of mutants of a
conserved histidine in the metallophosphatases calcineurin and l protein
phosphatase\' (1997) JBC 272:21296.\
4. Yu. L. et al. \'Spectroscopic and enzymatic characterization of the
active site dinuclear metal center of calcineurin: Implications for a
mechanistic role\' (1997) Biochemistry 36:10727.\
5. Rusnak, F. et al. \'Interaction of Bacteriophage l Protein
Phosphatase with Mn(II): Evidence for the Formation of a \[Mn(II)\]2
Cluster\' (1999) Biochemistry 38:6943.\
6. Hoff, RH et al. \'The Transition State of the Phosphoryl Transfer
Reaction Catalyzed by the Lambda Ser/Thr Protein Phosphatase\' (1999)
JACS 121:6382.\
7. Reiter, T. et al. \'Redox Regulation of Calcineurin in
T-Lymphocytes\' (1999) JBIC, 4:632\
8. Rusnak, F. \'The Manganese Activated Phosphatases\' in Metal Ions in
Biological Systems, Volume 37, Sigel, A. and Sigel, H., editors, Marcel
Dekker, Inc., New York, 2000, 305.\
9. Rusnak, F. \'Calcineurin: Form and Function\' (2000) Physiological
Reviews, in press.\
KatG in Isoniazid Activation and Resistance:

1\. Wengenack, NL. et al. \'Recombinant Mycobacterium tuberculosis
KatG(S315T) is a competent catalase-peroxidase with reduced activity
toward isoniazid\' (1997) J. Infect. Disease 176, 722.\
2. Wengenack, NL. et al. \'Evidence for Differential Binding of
Isoniazid by M. tuberculosis KatG and the Isoniazid-Resistant Mutant
KatG(S315T)\' (1998) Biochemistry 37, 15825.\
3. Wengenack, NL. et al. \'Mycobacterium tuberculosis KatG is a
Peroxinitritase\' (1999) Biochem. Biophys. Res. Comm. 256, 485.\
4. Wengenack, NL. et al . \'Isoniazid Oxidation by Mycobacterium
tuberculosis KatG: A Role for Superoxide Which Correlates with Isoniazid
Susceptibility\' (1999) JACS 121, 9748.

**Jose-Luis Sagripanti, PhD, Research Chemist, Molecular Biology Branch
(HFZ-113), Food and Drug Administration.** Part of my work involving
metal ions was summarized in \"DNA Damage mediated by metal ions with
special reference to copper and iron\" Chapter 6 In: Metal Ions in
Biological Systems Vol 36, pp.179-209, A Sigel & H Sigel, Eds. Marcel
Dekker, Basel, 1999. My interest focuses on metal ions as antimicrovials
for therapy and decontamination. References of my publications involving
metals and microorganisms, including HIV, Herpes, hemorrhagic viruses,
twelve bacterial pathogens, and bacterial spores, can be retrieved from
MEDLINE. I have monitored the Human Genome for the FDA since 1988,
recommended funding of DNA diagnostics as board member of Tools for
Diagnostics ATP-NIST since 1994, and involved in biological warfare and
antibioterrorism activities.

**Daniela Salvemini, PhD, Director of Biology, , MetaPhore
Pharmaceuticals.** Dr Salvemini received her PhD in Pharmacology in 1990
from the University of London training at the William Harvey Research
Institute under the mentorship of Prof. Sir John Vane. Scientific
reseach over her postdoctoral fellowship at Monsanto led to the
discovery that cyclooxygenase enzymes are receptor targets for the
actions of nitric oxide in inflammation. Dr Salvemini joined Searle in
1994 where she took the position of lead pharmacologist in the nitric
oxide synthase project evaluating the roles of nitric oxide in
inflammation and co-project leader in the Peroxynitrite decomposition
decomposition catalyst project assessing the therapeutic potential of
these metal-based agents as therapeutics for inflammatory diseases. In
1997 she became the project leader for the Superoxide dismutase mimetic
project at Searle. She has become one of the world leaders experts in
free radical biology and has published over 40 papers in this area,
co-authored several review articles and book chapters on the
pharmacology of nitric oxide, prostaglandins and free radicals. She has
received several International Awards including the 1997 Novartis Award
in Pharmacology. She is currently Director of Biology at MetaPhore a
metal-based company committed in development of metal-based entities as
therapeutic agents. Dr Salvemini\'s latest publication was in Science,
1999, 286,304-306 describing the identification of M40403, one of
Metaphore\'s lead small molecular weight synthetic manganese containing
superoxide dismutase mimetic as a stable and potent anti-inflammatory
and cytoprotective agent in vivo.Her past and present scientific
interests are in the field of inflammation and development of novel
anti-inflammatory agents for acute and chronic purposes

**Elliott Schiffmann, PhD, Scientist Emeritus, Lab. of Pathology,
National Cancer Inst., NIH.** Focus is on elucidating molecular events
in metastasis. We are studying the biochemistry of migration of
malignant cells, a critical feature of their dissemination from a
primary tumor site. A recent publication is that of Mulvaney et al., in
Int. J. of Cancer,78 (46-52), 1998.

**Joel P. Schneider, PhD, Assistant Professor of Chemistry and
Biochemistry, Chemistry and Biochemistry, University of Delaware.**
University of Pennsylvania, Dept. of Biochemistry and Biophysics
(1996-1999). Texas A&M University, Dept. of Chemistry, Ph.D. (1995). We
are currently interested in developing peptidic conformational
constraints based on lanthanide chelation. Methodology which will allow
linear peptides of biological interest to be constrained into their
bioactive conformation via lanthanide chelation should afford protein
specific probes whose action can be monitored by luminescence. We hope
to extend this work in order to develop Gadolinium-based constraints
which can be used as probes for MRI.

**Mary Sexton, PhD, Professor, Department of Epidemiology, U Of Maryland
School of Medicine.** My colleagues and I completed a study of
biomarkers of low-level exposure to lead. Data on the role of nutrition
and blood lead levels were published. Am currently conducting a primary
prevention of lead poisoning study randomized clinical trial that
enrolls pregnant women. The intervention is of health risk informtion
and skills in household cleaning to minimize exposure to the infant.

**Rass M. Shayiq, PhD, Scientific Review Administrator, NIH, Council for
Scientific Research.** 1997-present:Assist Prof, Dept of Medicine and
Biochemistry and Mol. Pharmacology, Thomas Jefferson University,
Philadelphia; 1999-present:Scientific Review Administrator (under
Interagency Personal Agreement); ALTX-4 study section, CSR, NIH. Past
and Present Research Intersts:Fluoride toxicity in GI tract; Biochemical
and molecular characterization of hepatic mitochondrial P450s;
regulation of sterol 27-hydroxylase; acetaminophen hepatotoxicity and
autoprotection\
Publications:\
1. Rass M. Shayiq, Dean W. Roberts, Kenneth Rothstein, John. E. Snawder,
Wayne Benson, Xiang Ma, and Martin Black (1999) Repeat exposure to
incremental doses of acetaminophen provides protection against
acetaminophen induced lethality in mice: An explanation for high
acetaminophen dosage in man without hepatic injury. Hepatology. 29,
451-463\
2. Rass M. Shayiq (1997) Role of gene overlap in the regulation of mRNA
translation for mitochondrial cytochrome P450c27/25 from the rat. J.
Biol. Chem. 272, 4050-4057

**Arthur S. Sherman, PhD, Senior Investigator, MRB, NIDDK.** I am a
mathematical modeler working in biophysics of insulin secretion. I am
interested in diabetes, and specifically in the sessions on Chromium and
Vanadium, which have been touted in the popular press as treatments.

**Roman Shimanovich, Graduate Student, Department of Chemistry,
Princeton University.** B.S. 1997 MIT; M.A. 1999 Princeton University;
PhD Advisor: Professor JT Groves. The focus of my graduate work have
been mechanistic studies of peroxynitrite decomposition, catalyzed by
water-soluble iron porphyrins.

**Karn Sorasaenee, Graduate Assistant, Chemistry, Texas A&M
University.** My research interest spans over the area of bioinorganic
chemistry. My current research, however, focuses on the studies of
anticancer active dinuclear metal complexes.

**Ashok Srivastava, MD, Associate Professor of Medicine and Head
Lab.Cell Signaling, Res. Center, CHUM-Hotel-Dieu, University of
Montreal.**

Publications on Vanadium, Insulinomimesis and Diabetes\
1. D\'Onofrio, F., Le, M.Q.U., Chiasson, J.-L., and Srivastava, A.K.:
Activation of mitogen activated protein (MAP) kinases by vanadate is
independent of insulin receptor autophosphorylation. FEBS Lett. 340:
269-275, 1994.\
2. Srivastava, A.K.: Potential use of vanadium compounds in the
treatment of diabetes mellitus. Expert Opinion on Invetigational Drugs
4: 525-536, 1995.\
3. Pandey, S.K., Chiasson, J.-L., and Srivastava, A.K.: Vanadium salts
stimulate mitogen-activated protein (MAP) kinases and ribosomal S6
kinases. Mol. Cell Biochem. 153: 69-78, 1995.\
4. St-Louis, J., Sicotte, B., Breton, E., and Srivastava, A.K.:
Contractile effects of vanadate on aorta rings from virgin and pregnant
rats. Mol. Cell Biochem. 153: 145-150, 1995.\
5. Pandey, S.K., Anand-Srivastava, M.B., and Srivastava, A.K.: Vanadyl
sulfate-stimulated glycogen synthesis is associated with activation of
phosphatidylinositol 3-kinase (PI3-K) and is independent of insulin
receptor tyrosine phosphorylation. Biochemistry 37: 7006-7014, 1998.\
6. Srivastava, A.K.: Use of pharmacological agents in elucidating the
mechanism of insulin action. Trends Pharmacol. Sci. 19: 205-209, 1998.\
7. Pandey, S.K., Théberge, J.-F., Bernier, M., and Srivastava, A.K. :
Phosphatidylinositol 3-kinase requirement in activation of the
ras/C-raf-1/MEK/ERK and p70s6k signaling cascade by the insulinomimetic
agent vanadyl sulfate. Biochemistry 38: 14667-14675, 1999.\
8. Srivastava, A.K.: Antidiabetic and toxic effects of vanadium
compounds. Mol. Cell. Biochem. 206: 177-182, 2000.\
9. Srivastava, A.K., Chiasson, J.-L., and Pandey, S.K.: Mechanism of
insulin-like actions of vanadium compounds. In: Metal Ions in Biology
and Medicine 4: 328-330, 1996, edited by P. Collery, J. Corbella, J.L.
Domingo, J.C. Etienne, J.M. Llobet, John Libbey Eurotext, Paris.\
10. Chiasson, J.-L., Srivastava, A.K.: Effets insulinomimétiques du
vanadium et autres ions métalliques. Utilisation potentielle dans le
traitement du diabète. In: Journées annuelles de diabétologie de
l\'Hôtel-Dieu 1999, J.L. Selam, Éditeur. Médecine-Sciences Flammarian,
Paris, 1-261, 1999.\
11. Théberge, J.-F., Pandey, S.K., and Srivastava A.K.: Protein tyrosine
phosphatase inhibitor vanadyl sulfate prolongs insulin-induced
activation of mitogen-activated protein kinases ERK 1/ERK 2 and
phosphatidylinositol 3-kinase. In: Pharmacology and Therapeutics in the
New Millenium, Gupta, S.K., Ed., Narosa Publishing House, New Delhi,
India.

**Ivan Stangel, MD, President & Director of Research, , BioMat
Sciences.** Former professor at McGill University, Faculty of Dentistry;
founder of BioMat Sciences, a spin-off from Lab for Biomaterials
Sciences; interest in biomaterials, interfaces; currently working on
metal-polymer bonds as a platform technology for new materials and
therapeutics.\
Citations:\
1. Di Renzo M, Ellis TH, Sacher E, Stangel I. A Photoacoustic FTIR Study
of the Chemical Modifications of Human Dentin Surfaces: I.
Demineralization. Biomed Mats Res (submitted)\
2. El Feninat F, Ellis TH, Sacher E, and Stangel I. A tapping mode AFM
study of collapse and denaturation in dentinal collagen. Dent Maters
(submitted)\
3. Breschi L, Gobbi P, Mazzotti G, Ellis T, Sacher E, Stangel I. A Field
Emission In-Lens SEM Study of Enamel and Dentin. J Biomed Maters Res 46:
315-323, 1999\
4. M. Di Renzo, F. El Feninat, B. Jiménez-Esquivel, S. Poulin, M.
Yavari, J. Xu, T.H. Ellis, E. Kruus, E. Sacher and I. Stangel. Adhesion
to dentin: The role of chemical reactions in surface modification.
Canadian Journal of Chemistry 76: 1-6, 1998.\
5. El Feninat F, Poulin S, Ellis TH, Sacher E, and Stangel I.
Moisture-dependent renaturation of collagen in phosphoric acid-etched
human dentin. J Biomed Mats Res 42: 549-55, 1998\
6. Xu J, Butler IS, Gilson DFR, Stangel I. FT-Raman and High-Pressure IR
Investigation of a Dental Composite. Biomats 18: 1653-1657, 1997

**Pamela E. Starke-Reed, PhD, Deputy Director, DNRC, NIDDK, NIH,
Division of Nutrition Research Coordination.** Recently moved from the
NIA - Program Director for: Nutriton and Metabolism, and Protein
Structure and Function portfolios in the Biology of Aging program. PhD
in Pathology, Research interestes:free radical biochemistry, oxidative
stess, protein oxidation, proteolysis, structural biology.\
Recent publications:\
1. Starke-Reed, P.E. Oxygen Radicals and Aging. In Oxygen Radicals and
the Disease Process. (Thomas , C.E. and Kalyanaraman, B. Eds.) Harwood
Academic Publishers, Reading England, 1997, pp 65-84.\
2. Starke-Reed, P.E.Protein Oxidation. In Methods in Aging Research.
(Yu, B.-P., Ed.) CRC Press Methods in the Life Sciences Series. 1998, pp
637-656.

**Ethan Dane Sternberg, Research Associate, Chemistry, University of
British Columbia.** I am a researcher working with Prof. David Dolphin
at the University of Brtish Columbia. Presently, I am also attached to
QLT Phototherapeutics. For the most part these therapeutic compounds are
porphyrin base materials. Since we are interested in extending their
therapeutic index beyond the area of PDT, I am interested in updating
myself in the field of organometallic therapeutic agents. Furthermore,
Prof. Dolphin can\'t make the conference and would like to have some
presence at it. References:

1\. Porphyrin-based photosensitizers for use in photodynamic therapy.
Sternberg ED, Dolphin D, Bruckner C, TETRAHEDRON 54: (17) 4151-4202 APR
23 1998.\
2. A novel stepwise degradation of porphyrins. Synthesis and structural
characterization of meso-tetraphenylchlorophinato nickel(II) and
meso-tetraphenylsecochlorinato nickel(II) Bruckner C, Sternberg ED,
MacAlpine JK, Rettig SJ, Dolphin D, JOURNAL OF THE AMERICAN CHEMICAL
SOCIETY 121: (11) 2609-2610 MAR 24 1999.\
3. Organometallic complexes of benzoporphyrins. Sternberg ED, Dolphin D.
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 213: 179-INOR, Part
2 APR 13 1997

**R. Subramanian, PhD, Director, R&D, Best Medical International.**
Research Interests: Radiopharmaceuticals for cancer Diagnosis and
Therapy, Delivery Systems, Brachytherapy Sources for Oncology and
Cardiology Applications Publications (Selected):

1 Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal
cancer with technetium 99m labeled totally human monolconal antibody
88BV59: Results of pivotol phase III multicenter studies, A Serafini et
al., Journal of Clinical Oncology, 16: 1777-87 (1998)\
2. Indium-111 labeled IgM, a human monoclonal antibody for infection
imaging: Preclinical studies in rats and rabbits. R. Subramanian, et
al., Journal of Nuclear Medicine, 38: 1054-1058 (1997).

**Anne O. Sumers, PhD, Professor, Microbiology, The University of
Georgia.** Many metals are essential in biology as active site cofactors
in metalloenzymes and as structural elements and/or inducers for key
regulatory proteins in both prokaryotes and eukaryotes. However metals,
such as mercury, are extremely toxic. We study the bacterial mercury
resistance (mer) operon, using molecular genetics and biochemistry to
elucidate the interactions of the transcriptional repressor/activator,
MerR, with metals, with DNA, and with RNA polymerase.\
1. Caguiat, J.J. et al. 1999. Cd(II)-responsive and constitutive mutants
implicate a novel domain in MerR. J.Bacteriol. 181:3462-3471.\
2. Kulkarni, R., and Summers, A.O. 1999. MerR cross-links to the and
alpha, sigma-70, and beta\'subunits of E.coli RNA polymerase in the
pre-initiation complex at the merTPCAD promoter. Biochemistry
38:3362-3368.\
3. Zeng, Q., et al. 1998. The core metal-recognition domain of MerR.
Biochemistry 37:15885-15895.

**Lawrence P. Szajek, PhD, Research Chemist, Cycoltron Facility,
NIH/CC/NMD/PET.** Research chenist at the clinical center cyclorton
facility. Responsible for the product of radiisotopes and
radiopharmaceuticals for for PET studies.

**Cha-Mei Tang, PhD, President, , Creatv MicroTech, Inc.** I am
interested in application to diagnositic x-ray imaging and disposable
testing. I am currently funded by NIH SBIR to develop x-ray anti-scatter
grids for mammography.

**Katherine H. Thompson, PhD ,Senior Research Associate, Chemistry
Department, The Medicinal Inorganic Chemistry Group.** Katherine
Thompson did her undergraduate studies in chemistry-zoology at Pomona
College, and her M.Sc. (1977) and Ph.D. (1991) degrees at the University
of British Columbia. Her M.Sc. dissertation work was on HbA1c as a
measure of diabetic control and her Ph.D. work, on manganese deficiency
effects in experimental diabetes. Her interest in vanadium as a
therapeutic adjunct in diabetes began with a postdoctoral fellowship
with John McNeill from 1991 until 1994. She then took up a research
fellowship in the Western Human Nutrition Research Center, Agricultural
Research Service, USDA, San Francisco, working on mathematical modeling
of trace mineral metabolism. Since 1996, she has been a senior research
associate in the Department of Chemistry at the University of British
Columbia, in the Medicinal Inorganic Chemistry Group, directed by Chris
Orvig.\
1. K.H. Thompson (1999) Vanadium and diabetes, BioFactors, 10: 43-51.\
2. K.H. Thompson, J.H. McNeill, and C. Orvig (1999) Vanadium compounds
as insulin mimics, Chem. Rev. 99: 2561-2572.\
3. K.H. Thompson, V.G. Yuen, J.H. McNeill, and C. Orvig (1998), Chemical
and Pharmacological Studies of a New Class of Antidiabetic Vanadium
Complexes, In: Vanadium Compounds. Chemistry, Biochemistry, and
Therapeutic Applications. A. S. Tracey and D. C. Crans, Eds., ACS
Symposium Series, Vol. 711, Chap. 26: 329-343 American Chemical
Society.\
4. K.H. Thompson, J.H. McNeill, and C. Orvig (1999), Vanadium-containing
Insulin Biomimetic Drugs, In: Topics in Biological Chemistry. Vol. 2:
Metallopharmaceuticals, M.J. Clarke and P.J. Sadler, Eds., Chap. 4:
139-158, Springer-Verlag, Heidleberg.\
5. K.H. Thompson, M. Battel and J.H. McNeill (1998) Toxicology of
vanadium in mammals, In: Vanadium in the Environment. Part 2. Health
Effects, Nriagu, J. O., Ed., Vol. 31, Chap. 2: 21-37, John Wiley & Sons,
Inc., NY.

**Belgaum S. Thyagaraja, PhD, Director, Molecular Biology Division, Gene
Probe Technologies, Inc..** Main areas of Research ionterests are:
DNA-RNA antisense technolgies, Development of Therapeutic antisense
molecules, immunochemical chemical assays for gene expression. Total ten
years experience in the field of Neuropeptides,, nurons isolation and
purifications. Published nearly 25 papers in the peer reviewed
International Journals.

**Dat Tran, PhD, Director, Chemistry, Princeton University.** PhD, UC
Santa Barbara (inorganic spectroscopy); Postdoc 98-present in Prof. Tom
Spiro\'s lab at Princeton. Research involves using Raman spectroscopy to
study metalloproteins/enzymes (B12 and related).

**Ah-lim Tsai, PhD, Associate Professor, Internal Medicine, Hematology
Division, University of Texas Houston Medical School.** Metelloenzymes,
esp. Hemeproteins; Electron transfer and redox reactions; Enzyme
kinetics, mainly transient kinetics (stopped-flow, rapid-freezing and
rapid quench); Computer modeling and simulation; Bioenergetics;
Mitochondria (structure and function); Membrane-bound proteins;
Prostaglandins, receptors, binding proteins and signal transduction;
Prostaglandin H synthase and nonsteroidal anti-inflammatory agents;
Nitric oxide and nitric oxide synthase; Spectroscopic methods (UV-VIS,
fluorescence, EPR and MCD).

Recent Publications:\
1. Tsai, A.-L., Berka, V., Kulmacz, R.J., Wu, G., and Palmer G. An
improved sample packing device for rapid freeze-trap EPR kinetic
measurements. Anal. Biochem. 264, 165-171, 1998.\
2. Ledvina, P. S., Tsai, A.-L., Wang, Z., Koehl, E., and Quiocho, F. A.
Dominant role of dipolar interactions in phosphate binding to a receptor
cleft with an electronegative charge surface: equilibrium, kinetic and
crystallographic studies. The Prot. Sci. 7, 2550-2559, 1998.\
3. Chen, P.-F., Berka, V., Tsai, A.-L., and Wu, K. K. Effects of D369
and R372 mutations on heme environment and function in human endothelial
nitric oxide synthase. J. Biol. Chem. 273, 34164-34170, 1998.\
4. Hsu, P.-Y., Tsai, A.-L., Kulmacz, R. J., and Wang, L.-H. Expression,
purification and spectroscopic characterization of human thromboxane
synthase. J. Biol. Chem. 274, 762-769, 1999.\
5. Wu, G., Wei, C., Kulmacz, R.J., Osawa, Y., and Tsai, A.-L.: A
mechanistic study of self-inactivation of the peroxidase activity in
prostaglandin H synthase-1. J. Biol. Chem. 274,9231?9237, 1999.\
6. Lu, G., Tsai, A.-L., van Wart, H.E., and Kulmacz, R.J.: Comparison of
the peroxidase reaction kinetics of prostaglandin H synthase-1 and -2.
J. Biol. Chem. 274, 16162-16167, 1999.\
7. Tsai, A.-L., Wu, G., Palmer, G., Bambai, B., Koehn, J.A., Marshall,
P.J., and Kulmacz, R.J. : Rapid kinetics of tyrosyl radical formation
and heme redox state changes in prostaglandin H synthase-1 and -2. J.
Biol. Chem. 274, 21695-21700,1999.\
8. Négrerie, M., Berka, V., Vos, M.H., Liebl, U., Lambry, J.-C., Tsai,
A.-L., and Martin, J.-L.: Geminate recombination of nitric oxide to
endothelial NO-synthase and mechanistic implications. J. Biol. Chem.
274, 24694?702, 1999.\
9. Shi, W., Hoganson, C.W., Espe, M., Bender, C.J., Babcock, G.T.,
Palmer, G., Kulmacz, R.J. and Tsai, A.-L.: EPR and ENDOR spectroscopic
identification and characterization of the tyrosyl radicals in
prostaglandin H synthase-1. Biochemistry 39, 4112-4121, 2000.

**Ravi K. Varma, PhD, Chemist and Project Officer, Drug Synthesis and
Chemistry Branch, National Cancer Institute.** I have been involved for
29 years in medicinal chemistry and drug development as both a scientist
and science administrator and currently works as a drug development
chemist at NCI. We interact very closely and actively with our
colleagues in biology and medicine, and with the academic community
facilitating the complex process of drug discovery and development.

**Anil Verma, PhD, Postdoc fellow, LCMB, NIH.** Research Interests:
Trace elemental analysis in bilogical tissues

**Ronald E. Viola, PhD, Professor, Department of Chemistry, University
of Akron.** BS, Chemistry, 1967, Fordham University; MS, Chemistry,
1973, Penn State Univ.; Ph.D., Biochemistry, 1976, Penn State Univ.;
Postdoc., 1976-79, Univ. of Wisconsin; Asst. Prof., 1979-84, S. Illinois
Univ. Assoc. Prof., 1984-89, Univ. of Akron; Prof., 1989- , Univ. of
Akron. My research interests include: Kinetic and mechanistic studies of
enzyme-catalyzed reactions. Examination of enzyme mechanisms by chemical
modification, molecular modeling, and site-directed mutagenesis.
Magnetic resonance studies of metal complexes with biological ligands .
Introduction of unnatural amino acids into enzymes. High resolution
structural studies of biomolecules.

**Angela Wilks, MD, Assistant Professor, Department of Pharmaceutical
Sciences, University of Maryland.** Previous position: Adjunct Assistant
Professor (1995-1998) Department of Pharmaceutical Chemistry, University
of California San Francisco. Previous research involved the relationship
of structure to function in hemeproteins. Particular focus included the
characterization and elucidation of the mechanism of action of heme
oxygenase, the rate limiting enzyme in heme degradation. Current
Research: The focus of my current research is the acquisition and
utilization of heme by bacterial pathogens such as Shigella dysenteriae,
Vibrio cholerae and Corynebacterium diphtheriae. Iron is essential for
the survival of all bacteria and many pathogenic bacteria have developed
sophisticated mechanisms by which they utilize\
the hosts heme containing proteins as a source of iron. The ability of
pathogenic bacteria to acquire iron is in part linked to their
virulence. The goal of the project is to characterize critical proteins
involved\
in the acquisition and utilization of heme. Understanding the mechanism
of heme uptake and iron release at the molecular level will allow
rational design of therapeutic agents for the treatment of bacterial
infections.\
Publications:\
1. Angela Wilks and Pierre Moenne-Loccoz \"Identification of the
Proximal Ligand His-20 in Heme Oxygenase (Hmu O) from Corynebacterium
diphtheriae.\" J. Biol. Chem. (In press)\
2. David J. Schuller, Angela Wilks, Paul R. Ortiz de Montellano, and
Thomas L. Poulos, \"Crystal Structure of human heme oxygenase.\" Nat.
Struc. Biol. (1999) 6, 860-867.\
3. Angela Wilks, and Michael P. Schmitt, \"Expression and
Characterization of a Heme Oxygenase (HmuO) from Corynebacterium
diphtheriae\" J. Biol. Chem. (1998) 273, 837-841.\
4. Angela Wilks, and Paul Ortiz de Montellano, \"Heme Oxygenase (HO-1):
Covalent Modification of the Enzyme by Heme during the Reduction of
CBrCl3\" Biochemistry (1998) 37, 2889-2896.

**Gail R. Willsky, PhD ,Associate Professor, Biochemistry, SUNYat
Buffalo Sch.of Med.and Biomedical Science.** S.B. in Biophysics, MIT;
Ph.D. Micobiology Tufts, University; Postdoctoral - Harvard University
(Advisor G. Guidotti). Research Interests - Role of oxovanadium
compounds in metabolism, role of metals in alleviating symptoms of
Diabetes. Biochemistry, genetics magnetic resonance spectrometry, cell
biology and clinical studies are used to study S.cerevisiae as a model
system, rats with STZ induced diabetes and human patients with NIDDM.

Recent papers:

1\. Willsky, G.R, Goldfine, A.B., and Kostyniak, P.J.(1998) Pharmacology
and toxicology of oxovanadium species, ACS Symposium Series 711,
pp278-296;

2\. Goldfine, A.B., Patti, M-E., Zuberi, L, Goldstein, B.J., LeBlanc,
R., Landaker, E.J, Jiang, Z.Y., Willsky, G.R., and Kahn, C.R. (2000)
\"Metabolic Effects of Vandyl Sulfate in Humans with NIDDM Diabetes
mellitus: in vivo and in vitro studies\" Metabolism 49: 400-410.

**Mary K. Wolpert, PhD ,Chief, Grants & Contracts Operations Branch,
Division of Cancer Treatment & Diagnosis, National Cancer Institute.**
Mary K. Wolpert is the Chief of the Grants and Contracts Operations
Branch (GCOB), Developmental Therapeutics Program, Division of Cancer
Treatment and Diagnosis, National Cancer Institute. In this role, she
and GCOB Program Directors monitor a portfolio of grants and cooperative
agreements in the area of preclinical drug development. GCOB also serves
as a focal point for the administration of contracts for the
Developmental Therapeutics Program. Major themes of current research
include the discovery of new drugs from natural products, including
plant, marine, and microbial sources, traditional medicinal chemistry
approaches, and new combinatorial and structure-based methods; the
development of new treatment strategies, such as gene therapy; selective
targeting of therapies using biodegradable biopolymers, liposomes, and
antibodies; development of new preclinical models for the evaluation of
therapies for specific diseases, such as breast cancer, prostate cancer,
or AIDS-related malignancies; studies on the pharmacology, toxicology,
and mechanisms of anticancer drug action; studies on understanding,
preventing, and overcoming drug resistance; and studies to promote drug
discovery and development based on molecular targets. Dr. Wolpert
received her Ph.D. degree from the University of Michigan in Ann Arbor,
Michigan. She is the author of 40 publications in the areas of
anticancer drug discovery and development.

**Willaim H. Woodruff, PhD ,Laboratory Fellow, Bioscience Division, Los
Alamos National Lab.** William H. Woodruff received the B.A. in
Chemistry from Vanderbilt University in 1962. Following five years in
the U. S. Navy he began graduate work at Purdue University and earned
the M.S. (1969) and Ph.D. (1972). In 1972-74 he held a NIH Postdoctoral
Fellowship at Princeton University. His current position is Laboratory
Fellow in the Michelson Resource, Bioscience Division, Los Alamos
National Laboratory. Significant Past Positions: Assistant Professor of
Chemistry, Syracuse University, 1974-77; Assistant (1977-1980) and
Associate (1981-84) Professor of Chemistry, The University of Texas at
Austin; Visiting Associate at CalTech, 1982; Visiting Professor at The
University of North Carolina, 1983. Significant Awards and Recognitions:
National Institutes of Health Postdoctoral Fellowship, 1972-74;
Laboratory Fellow, Los Alamos National Laboratory, 1990-present; Chair,
NIH Molecular and Cellular Biophysics (BBCA) Study Section, 1989-91;
Co-recipient, R&D 100 Award for development of the Ultrafast Infrared
Spectrometer, 1993; Bomem-Michelson Award presented by the Coblentz
Society for outstanding achievements in Spectroscopy, 1997; Elisabeth
Roberts Cole Award presented by the Biophysical Society for outstanding
achievements in Biophysics, 1997; Distinguished Alumnus Award, Purdue
University School of Science, 1998. Research interests: Structural
dynamics of inorganic and biological systems; Spectroscopy, dynamics and
function of redox metalloproteins; Photophysics and photochemistry of
transition metal complexes; Biological and photochemical energy
transduction; Fast events in protein folding; Advanced laser techniques;
Vibrational and time-resolved spectroscopies; Vibrational hyperspectral
imaging.

**Edward Wu, PhD, Postdoctoral research, Drug Resistance Program,
National Cancer Institute.**

Previous Position:Postdoctoral Research in Biocrystallography Laboratory
and Department of and Microbiolog University of Georgia, Athens.
Previous research: Research interests include the biochemical
characterization and crystal structure determination of (1) the novel
protein \'augmenter of liver regeneration (ALR)\', and (2) the
membrane-associated human ferrochelatase which is the terminal enzyme in
the heme biosynthesis pathway. I have solved the crystal structure of
ALR using the Se-MAD (multiple anomalous diffraction) method and the
structure of human ferrochelatase by single anomalous scattering (SAS)
from iron atoms. ( to be published in Nature Structural Biology, June,
2000). The metals in the cluster and the binding site are the center
interest of this enzyme

**Annette B. Wysocki, PhD, Laboratory Chief, Wound Healing Laboratory,
NIH.** Dr. Annette Wysocki is currently Chief of the Wound Healing
Laboratory. Her area of research interest is in the degradation of
extracellular matrix in chronic wounds. Her research in chronic wounds
has revealed the degradation of fibronectin in chronic wounds, the
presence of active fibronectin degrading proteases in chronic wound
fluids. Subsequent studies have identified that there are elevated
levels of matrix metalloproteinases (MMP\'s) in chronic wounds. And that
in both acute and chronic wounds there is a decrease in the expression
of MMP-9 with progression to healing. Recent studies have also detected
the presence of active urokinase plasminogen activator (uPA) in chronic
wound fluid that become inhibitor bound with progression to healing.

**Jenny J. Yang, Ph.D. , Assistant Professor, Department of Chemistry,
Georgia State University.**

B.S., 1982, Xiangtan University, China; M.S., 1985, Xiangtan University,
China; Ph.D., 1992, Florida State University (advisor: Dr. Harold van
Wart); Postdoctoral Research Fellow, 1992-1993, Syntex Discovery
Research (Roche Bioscience); Oxford Center for Molecular Sciences
Postdoctoral Research Fellow, 1993 -1995, University of Oxford, UK
(advisor: Drs. Christopher M Dobson and Sheena E. Radford); Donahue
Postdoctoral Research Fellow, 1996, Yale University (advisor: Dr. Lynne
Regan); 1997-Present, Assistant Professor of Biochemistry, Georgia State
University. Research Interests: design and analysis of calcium binding
proteins with tailored functions; understanding conformational
flexibility of cell adhesion molecules.

**Jeffrey M. Zaleski, PhD, Assistant Professor, Chemistry, Indiana
University.** Our research is based in the design of novel
photoactivatable transition metal complexes for potential Photodynamic
Therapy Applications. The systems under current investigation include
transition-metal diazo and enediyne compounds that use diradical
generation to perform H-atom abstraction from DNA. The goal of our work
is to not only understand the chemistry of these intriguing compounds,
but to potential design PDT agents for hypoxic environments. Citations:\
1. J.Chem. Soc., Chem. Commun. 1999, 2405.\
2. J.Chem. Soc., Chem. Commun. 2000, 69.\
3. J. Am. Chem. Soc. 2000, Web release 3/17/00.

**Tongqing Zhou, PhD, Research Associate, Biochemistry and Molecular
Biology, Wayne State University School of Medicine.** I am a
postdoctoral research associate at Dr. Barry Rosen\'s lab. Our research
is mainly focused on understanding the mechanisms

of metal resistance in cells. Currently, I am involved in the x-ray
crystallographic studies of an arsenite/antimonite-tanslocating ATPase.
See my web site for details.

**Steven J. Zullo, PhD, SSF, LBG-NIMH-NIH.** Mitochondrial biogenesis,
mutagenesis,and evolution.

REVISED LIST OF REGISTRANTS

Reflects all advance inquiries and on-site registrants\*

Michael J. Abrams, PhD

President and Chief Executive Officer

AnorMED, Inc.

20353 64th Ave, #200

Langley, BC V2Y 1N5

Canada

Ph: (604) 530-1057

Fax: (605) 530-0976

mabrams@anormed.com

Thomas Aigner, PhD\*

Science Administrator

Division of Neuroscience and Behavioral Research

National Institute on Drug Abuse

6001 Executive Blvd.

Room 4284, MSC 9555

Bethesda, MD 20892

USA

Ph: 301-435\--1314

Fax: Apr-43

ta17r@nih.gov

George Alexander

National Cancer Institute

USA

Ph: 301 435-9223

Carolyn J. Anderson, PhD

Associate Professor

Department of Radiology

Washington University School of Medicine

510 S. Kingshighway Blvd. Campus Box 8225

St. Louis, MO 63110

USA

Ph: (314) 362-8427

Fax: (314) 362-9940

andersoncj@mir.wustl.edu

Richard A. Anderson, PhD

Lead Scientist

USDA, Beltsville Human Nutrition Research

United States Department of Agriculture

Bldg 307, Room 224

Beltsville, MD 20705

USA

Ph: (301) 504-8091

Fax: (301) 504-9062

anderson@307.bhnrc.usda.gov

William H. Armstrong, PhD\*

Associate Professor

Chemistry

Boston College

Eugene F. Merkert Chemistry Center

2609 Beacon Street

Chestnut Hill, MA 02481-3860

USA

Ph: (617) 552-8077

Fax: (617) 552-2705

armstrow@bc.edu

http://chemserv.bc.edu/Department/faculty/armstrong/armstrong.html

Georgia M. Arvanitis, PhD

Professor

Chemistry

The College of New Jersey

2000 Pennington Rd

Ewing, NJ 8618

USA

Ph: 609-771-2917

Fax: 609-637-5157

arvanit@tcnj.edu

Bruce A. Averill, PhD

Professor

E. C. Slater Institute &

University of Amsterdam

Swammerdam Institute for Life Sciences

Plantage Muidergracht 12

Amsterdam, NH 1018 TV

NL

Ph: 31-20-525-5045

Fax: 31-20-525-5124

baa@chem.uva.nl

Ian Robert Baird, PhD

Research Scientist

Chemistry

AnorMED, Inc.

#200-20353 64th Ave.

Langley, BC V2Y 1N5

CAN

Ph: (604) 530-1057

Fax: (604) 530-0976

ibaird@anormed.com

Gurusamy Balakrishnan, PhD

Research Associate

Chemistry

Princeton University

Washington Road

Princeton, NJ 8544

USA

Ph: 609-258-3908

Fax: 609-258-3890

bala@princeton.edu

Radhakrishnan Balu\*

Consultant

Worldline Systems Inc

6509 Great Drum Circle

Columbia, MD 21044

USA

Ph: 410 531 7975

Fax:

worldline@home.com

Michele L. Barnard, PhD

Scientific Review Administrator

NIDDK, NIH

6707 Democracy Blvd.

Room 657, MSC 5452

Bethesda, MD 20892

USA

Ph: 301 594 8898

Fax: 301 480 3505

barnardm@extra.niddk.nih.gov

Anthony Barnes, PhD\*

Vice President

Immunicon

3401 Masons Mill

Huntingdon Valley, PA 19006

USA

abarnes@immunicon.com

Girish C. Barua, PhD MD\*

Technology Specialist

Office of Technology Transfer

National Institutes of Health

6011 Executive Blvd.

Suite 325

Rockville, MD 20852

USA

Ph: 301/496-7735

Fax: 301/402-0220

gbarua@od.gov

W. Douglas Bates, PhD

Business Development

Setanta Theapeutics Inc.

800 East Leigh Street

Suite 204

Viginia Biotechnology Park

Richmond, VA 23219

USA

Ph: (804)828-0276

Fax: (804)828-8599

wdbates@saturn.vcu.edu

Marjam G. Behar, PhD

Scientific Review Administrator

Center for Scientific Review

National Institutes of Health

6701 Rockledge Dr, Rm 4178

MSC 7806

Bethesda, MD 20892-7806

USA

Ph: 301-435-1180

Fax: 301-480-2327

beharm@csr.nih.gov

John A. Beisler, PhD\*

Program Director

Grants & Contracts Operations Branch

National Cancer Institute

Executive Plaza North, Room 841

6130 Executive Blvd

Bethesda, MD 20982-7456

USA

Ph: 301 496-8783

Fax: 301 402-5200

beislerj@exchange.nih.gov

Barbara Anne Bench

Graduate Student

Chemistry Department

Brown University

Box H

Providence, RI 2912

USA

Ph: (401) 863-7569

Fax: (401) 863-2594

barbara_bench@brown.edu

Mike Berardini, PhD

Adjunct Professor

Chemistry

The College of New Jersey

2000 Pennington Rd

Ewing, NJ 8628

USA

Ph: 609-771-2397

Fax: 609-637-5157

berardin@tcnj.edu

Lawrence J. Berliner, PhD\*

Professor

Chemistry

Ohio State University

100 W. 18th Ave

Columbus, oh 43210

USA

Ph: 614 292 0134

Fax: 614 292 1532

berliner.2@osu.edu

http://livers.mps.ohio-state.edu/

Andrew Cameron Beveridge

Graduate Student

Department of Chemistry

Brown University

324 Brook St. Box H

Providence, RI 2912

USA

Ph: 401 863-3169

Fax: 401 863-2594

andrew_beveridge@brown.edu

Hiranmoy Bhattacharjee, PhD

Assistant Professor-Research

Biochemistry and Molecular Biology

Wayne State University School of Medicine

540 East Canfield Avenue

Detroit, MI 48201

USA

Ph: (313) 577-0618

Fax: (313) 577-2765

<hbhattac@med.wayne.edu>

Ulrich Bierbach, PhD

Wake Forest University

Department of Chemistry

P.O. Box 7486 Reynolda Station

Winston-Salem, NC 27109

USA

Ph: 336 758-3507

Fax: 336 758-4656

bierbau@wfu.edu

Ofer Blum, PhD

Assistant Professor

University of Michigan

3074 Dow Bldg.

2300 Hayward St.

Ann Arbor, MI 48109-2136

USA

Ph: 734-763-8027

Fax: 734-763-0459

oferblum@umich.edu

http://www.engin.umich.edu/dept/cheme/people/blum/blum.html

Andrew S. Borovik, PhD

Associate Professor

Department of Chemistry

University of Kansas

Lawrence, KS 66045

USA

Ph: 785-864-4067

Fax: 785-864-5396

aborovik@ukans.edu

John L Bowers, PhD

Scientific Review Administrator

National Institutes of Health

6701 Rockledge Drive

MSC 7806

Bethesda, MD 20892

USA

Ph: 301 435-1725

Fax: 301 480-2327

jb333u@nih.gov

Michael K. Bowman, PhD\*

Staff Scientist

Macromolecular Structure & Dynamics

Pacific Northwest National Laboratory

PO Box 999

Richland, WA 99352-0999

USA

Ph: 509-376-3299

Fax: 509-376-2303

michael.bowman@pnl.gov

Barbara Brandys\*

Reference Librarian

ORS

NIH Library

Bldg. 10, 1L-19

10 Center Drive

Bethesda, MD 20892

USA

Ph: 301 594-6203

Fax: 301 402-0254

brandysb@mail.nih.gov

Martin W. Brechbiel, PhD\*

Section Chief

Radiation Oncology Branch

Radioimmune & Inorganic Chemistry

NIH

Building 10, Room B3B69

10 Center Drive

Bethesda, MD 20892-1002

USA

Ph: 301-496-0591

Fax: 301-402-1923

martinwb@box-m.nih.gov

Jorge Arturo Briones

Pre-IRTA

Metabolic Dieseases Branch

NIDDK

10 Center Dr., 3N116, MSC 1268

Bethesda, MD 20892

USA

Ph: 301-496-1388

Fax: 301-402-0014

jorge.briones@nih.gov

Pechimuthu J Britto, PhD

Research Fellow

Laboratory of Biochemistry and Genetics

NIDDK

BLDG. 8 / ROOM 2A-21

Bethesda, MD 20892

USA

Ph: 301-594-5194

Fax: 301-402-0240

jeramb@intra.niddk.nih.gov

Joan Broderick, PhD

Assistant Professor

Department of Chemistry

Michigan State University

414A Chemistry Building

East Lansing, MI 48824-1322

USA

Ph: (517) 355-9715

Fax: (517) 353-1793

broderij@cem.msu.edu

http://poohbah.cem.msu.edu/faculty/brodericjgrp/index.html

Simon R. Bruce, MD\*

Clinical Associate

Clinical Neurocardiology Section

Building 10, Room 6N252 MSC 1620

10 Center Blvd

Bethesda, MD 20892

USA

Ph: 301-435-6746

Fax: 301-402-0180

sbruce@box-s.nih.gov

Henry Bryant, PhD

Laboratory of Diagnostic Radiology Research

National Institutes of Health

Bldg. 10 Rm. B1N256

Bethesda, MD 20892

USA

Ph: null

Fax:

blh@helix.nih.gov

Jeff W.M. Bulte, PhD

Staff Scientist

Lab of Diagn Radiology Research

National Inst of Health

Building 10, B1N245

10 Center Dr MSC 1074

Bethesda, MD 20892

USA

Ph: 301-402-4547

Fax: 301-594-2979

jwmbulte@helix.nih.gov

John A. Bumpus, PhD

Professor of Chemistry

Chemistry

University of Northern Iowa

McCollum Science Hall

University of Northern Iowa

Cedar Falls, IA 50614

USA

Ph: 319-273-7220

Fax: 319-273-7127

john.bumpus@uni.edu

Richard M Burger, PhD

Chief Scientist

C/O Public Health Research Institute

Redox Pharmaceutical Corporation

455 First Avenue

New York, NY 10016

USA

Ph: 212-576-8428

Fax: 212-578-0804

burger@phri.nyu.edu

Benjamin J. Burke, PhD

Senior Scientist I

Computational Chemistry

Agouron Pharmaceuticals

10777 Science Center Drive

San Diego, CA 92121-1111

USA

Ph: (858) 622-3018

Fax: (858) 678-8244

burke@agouron.com

Cynthia J. Burrows, PhD

Professor of Chemistry

Department of Chemistry

University of Utah

315 S. 1400 East, Rm 2020

Salt Lake City, UT 84112-0850

USA

Ph: 801-585-7290

Fax: 801-585-7868

burrows@chemistry.utah.edu

http://www.chem.utah.edu/chemistry/faculty/burrows/burrows.html

Aldo Cagnolini

Researcher

Bracco Research USA

305 College Road East

Princeton, NJ 8540

USA

Ph: (609)-514-2431

Fax: (609) 514-2446

acagnoli@diag.bracco.com

Hui-Zhi Cai, PhD

Senior Scientist

Chemistry

Palatin Technologies

175 May St., Ste. 500

Edison, NJ 8837

USA

Ph: 732/225 3883

Fax: 732/346 0779

huizhicai@palatin.com

Beth R. Cameron, PhD

Senior Scientist

Chemistry

AnorMED Inc.

200-20353 64th Ave

Langley, BC V2Y 1N5

CAN

Ph: 604-530-1057

Fax: 604-530-0976

bcameron@anormed.com

James W. Canary, PhD

Associate Professor

Chemistry

New York University

100 Washington Sq E

New York, NY 10003

USA

Ph: 212-998-8422

Fax: 212-260-7905

james.canary@nyu.edu

http://www.nyu.edu/pages/canary/

James C Cassatt, PhD

Director, Division of Cell Biology and Biophysics

NIGMS

NIH

Building 45, Room 2AS19

Bethesda, MD 20892

USA

Ph: 301-594-0828

Fax: 301-480-2004

cassattj@nigms.nih.gov

Marvin Cassman, PhD

Director, National Institute of General Medical Sciences

Office of the Director

National Institute of General Medical Sciences

National Institutes of Health

45 Center Drive, MSC 6200

Bethesda, MD 20892-6200

USA

Ph: 301-594-2172

Fax: 301-402-0156

cassmanm@nigms.nih.gov

http://www.nigms.nih.gov

Ty Caudle, PhD

Assistant Professor

Chemistry and Biochemistry

Arizona State University

Box 871604

Tempe, AZ 85287-1604

USA

Ph: (480) 965-5178

Fax: (480) 965-2747

tcaudle@asu.edu

Winslow S. Caughey, PhD

Special Volunteer

Laboratory of Persistent Viral Diseases

NIAID,NIH

903 South Fourth Street

Hamilton, MT 59840

USA

Ph: 406-363-9440

Fax: 406-363-9286

wcaughey@nih.gov

Richard Chang, MD\*

Physician/ Interventional Radiologist

Radiology

WG Magnusson Clinical Center/ NIH

Bldg 10 Rm 1C-660

NIH Clinical Cneter

9000 Rockville Pike

Bethesda, Md 20892

USA

Ph: 301-402-0256

Fax:

rchang@cc.nih.gov

Madhuri Chattopadhyay

Graduate student

Chemistry and Biochemistry

University of Maryland, College Park

440, Ridge Rd, \# 11

Greenbelt, MD 20770

USA

Ph: 301-405-0373

Fax: 301-405-9376

madhuri@wam.umd.edu

Jennifer Cheek\*

Michigan State University

USA

cheek@cem.msu.edu

Hua Chen

National Cancer Institute

USA

P.B. Chock

National Institutes of Health

USA

Hyun-Soon Chong

National Cancer Institute

USA

Ph: 301 496-6027

Seema Choudhary, MD

Researcher

Chemistry

University at Buffalo

Department of Chemistry

NSM Complex, North Campus

University at Buffalo

Buffalo, NY 14260

USA

Ph: 716-645-6800

sc30@acsu.buffalo.edu

Michael J. Clarke, PhD

Professor

Chemistry

Boston College

Merkert Chemistry Center

Boston College

Chestnut Hill, MA 2467

USA

Ph: 617 552 3624

Fax: 617 552 2705

clarke@bc.edu

http://chemserv.bc.edu/Department/Faculty/Clarke/default.html

R. B. Clarkson

University of Illinois

Bioengineering

Illinois EPR Center

Urbana, IL 61801

USA

\(21\) 244-1375

\(217\) 244-1475

clarkson@uiuc.edu

Traci Clemons, PhD\*

Statistician

The EMMES Corporation

11325 Seven Locks Road

Suite 214

Potomac, MD 20854

USA

Ph: (301) 299-8655

Fax: (301) 299-3991

tclemons@emmes.com

Behor Cohen

NIAID

USA

Seth M. Cohen, PhD

Postdoctoral Fellow

Chemistry

M.I.T.

Dept. of Chemistry

Bldg. 18-528

Cambridge, MA 2139

USA

Ph: 617-253-1824

Fax: 617-258-8150

<smcohen@mit.edu>

James R. Connor, PhD\*

Professor and Vice-Chair

Department of Neuroscience & Anatomy, M.C. H109

Penn State University College of Medicine

Director, G.M. Leader Alzheimer\'s Disease Research

P.O. Box 850

Hershey, PA 17033

USA

Ph: (717) 531-8650

Fax: (717)-531-5184

jrc3@psu.edu

Max Costa, PhD

Professor and Chairman

Department of Environmental Medicine

NYU School of Medicine

550 1st Avenue

New York, NY 10016

USA

Ph: (914) 731-3515

Fax: (914) 351-2118

costam@env.med.nyu.edu

Rebecca Bortz Costello, PhD

Deputy Director

Office of Dietary Supplements

Office of the Director

National Institutes of Health

Bldg 31, Rm 1B25

Bethesda, MD 20892

301-435-2920

301-480-1845

<costellb@od.nih.gov>

http://odp.od.nih.gov/ods/default.html

James Cowan, PhD

Professor

Department of Chemistry

Ohio State University

100 West 18th Avenue

Columbus, OH 43210-1185

USA

Ph: (614) 292-2703

Fax: (614) 292-1685

cowan@chemistry.ohio-state.edu

John W. Cox, PhD

Research Associate

Chemistry Department

Virginia Commonwealth University

PO Box 842006

1001 W. Main St.

Richmond, VA 23284-2006

USA

Ph: (804)828-0276

Fax: (804)828-8599

che5jwc@titan.vcu.edu

Candace M. Coyle, PhD

Research Associate

Department of Chemistry

Princeton University

101 Frick Hall

Princeton, NJ 8544

USA

Ph: (609)258-3908

Fax: (609)258-3890

ccoyle@princeton.edu

Debbie C. Crans, PhD

Professor

Chemistry

Colorado State University

1301 Center Av.

Fort Collins, CO 80523

USA

Ph: 970-491-7635

Fax: 970-491-1801

crans@lamar.colostate.edu

Barbara Y. Croft, PhD\*

Program Director

Biomedical Imaging Program

NCI

6130 Executive Blvd

Suite 800

Rockville, MD 20852

USA

Ph: 301-496-9531

Fax: 301-480-5785

bc129b@nih.gov

http://www.nci.nih.gov/dip/

Alvin L. Crumbliss, PhD

Professor

Chemistry

Duke University

Box 90346

Durham, NC 27708-0346

USA

Ph: 919-660-1540

Fax: 919-660-1605

alc@chem.duke.edu

http://www.chem.duke.edu/research/alc/alc.html

Valeria Culotta, PhD

Associate Professor

Department of Environmental Health Sciences

Johns Hopkins University

School of Public Health

615 N. Wolfe St., Rm 7032

Baltimore, MD 21205-2103

USA

Ph: 410-955-3029

Fax: 410-955-0116

vculotta@jhsph.edu

Dory Cwikel, PhD

Visiting Research Staff

Chemistry Department

Princeton University

Frick Laboratory

Washington Road

Princeton, NJ 8544

USA

Ph: 609 2583908

Fax: 609 2583890

dcwikel@princeton.edu

Alison F. Davis, PhD

Science Writer

NIGMS

45 Center Drive

Room 1AS.25

Bethesda, MD 20892-6200

USA

Ph: 301.496.7301

Fax: 301.402.0224

davisa@nigms.nih.gov

Jeffery T. Davis, PhD

Chemistry and Biochemistry

University of Maryland

Chemistry 2102

College Park, MD 20742

USA

Ph: 301-405-1845

jd140@umail.umd.edu

http://www.chem.umd.edu/organic/davis.html

Mindy I. Davis

Graduate Research Assistant

Department of Chemistry

Stanford University

333 Campus Drive

Stanford, CA 94305-5080

USA

Ph: (650) 723-9343

Fax: (650) 725-0259

midavis@stanford.edu

http://www-chem.stanford.edu/\~midavis

Lopa Vrushank Desai,

Student

Chemistry

Connecticut College

Box 3451

Connecticut College

270 Mohegan Ave.

New London, CT 6320

USA

Ph: (860)-439-3508

lopadesai@hotmail.com

http://oak.conncoll.edu/\~lvdes

Tara M. DeSilva

Graduate Student

Department of Chemistry

University of Pennsylvania

231 South 34th Street

Philadelphia, PA 19104

USA

Ph: 215-898-3612

tdesilva@sas.upenn.edu

Daryl DesPres\*

Biologist

NMRF

NIH/NINDS

10/B1D69

Bethesda, MD 20892-1060

USA

Ph: 301-496-8141

Fax: 301-402-0119

despres@helix.nih.gov

Sergei Dikanov, PhD

Senior Research Scientist

Illinois EPR Center

University of Illinois at Urbana-Champaign

190 MSB, 506 S. Mathews Av.

Urbana, IL 61801

USA

Ph: (217) 333-37776

Fax: (217) 333-8868

dikanov@uiuc.edu

Kenneth J. Dillon, PhD\*

President

Spectrum Bioscience, Inc.

2020 F Street, N.W. #505

Washington, DC 20006

USA

Ph: 202-467-0572

kjdillon@erols.com

www.biophoton.com

G. Charles Dismukes, PhD\*

Professor

Chemistry

Princeton University

Hoyt Laboratory

Princeton, NJ 8544

USA

Ph: 609-258-3949

Fax: 609-258-1980

dismukes@princeton.edu

www.princeton.edu/\~catalase

Dabney W. Dixon, PhD

Professor of Chemistry

Department of Chemistry

Georgia State University

Department of Chemistry

Atlanta, GA 30303

USA

Ph: (404) 651-3908

Fax: (404) 651-1416

ddixon@gsu.edu

Susan R. Doctrow, PhD

Vice President, Research

Eukarion, Inc.

6F Alfred Circle

Bedford, MA 1731

USA

Ph: 781-275-0424

Fax: 781-275-0752

s.doctrow@eukarion.com

Tom Dowell, PhD\*

HSA

CSR

NIH

Room 2180, MSC 7818

Rockledge 2 Building

6701 Rockledge Drive

Bethesda, MD 20891

USA

Ph: 301-435-1169

Fax: 301-480-1171

dowellr@csr.nih.gov

Greg Downing\*

Office of the Director

National Institutes of Health

Bldg 1, Rm 218

One Center Drive

Bethesda, MD 20892

USA

Ph: 301-594-7740

Fax: 301-402-0280

gd34f@nih.gov

http://biomarkers.od.nih.gov/

Francis D\'Souza, PhD

Associate Professor

Chemistry

Wichita State University

1845, Fairmount

Wichita, KS 67260-0051

USA

Ph: 316-978-3120

Fax: 316-978-3431

dsouza@wsuhub.uc.twsu.edu

http://www.twsu.edu/\~chemwww/dsouza.html

Kim R Dunbar, PhD

Professor of Inorganic Chemistry

Chemistry

Texas A&M University

PO Box 30012

College Station, TX 77842-3012

USA

Ph: 979-845-5235

Fax: 979-845-7177

dunbar@mail.chem.tamu.edu

Rosalie Dunn, PhD\*

Program Director

Division of Heart and Vascular Diseases

National Heart, Lung, and Blood Institute

6701 Rockledge Drive MSC 7940

Bethesda, MD 20892-7940

USA

Ph: 301-435-0505

Fax:

dunnr@nhlbi.nih.gov

Joseph E Earley, PhD

Program Officer

Inorganic, Bioinorganic and Organometallic Chem.

National Science Foundation

4201 Wilson Boulevard

Arlington, VA 22230

USA

Ph: 703-306-1440

jearley@nsf.gov

http://www.georgetown.edu/earleyj/jeemain.html

Richard C. Elder, PhD

Professor

Chemistry, Biomedical Chemistry Research Center

University of Cincinnati

Department of Chemistry

University of Cincinnati

P.O. Box 210172

Cincinnati, OH 45221-0172

USA

Ph: 513.556.9224

Fax: 513.556.9239

Richard.Elder@UC.edu

http://knut.rvs.uc.edu/Chemistry/fac_staff/elder.html

Paul D. Ellis, PhD\*

Technical Group Leader in Magnetic Resonance

Environmetal Molecular Sciences; K8-98

Pacific Northwest National Laboratories

Battelle Boulevard

PO Box 999

Richland, WA 99352

USA

Ph: 509 372 3888

Fax: 509 376 2303

pd_ellis@pnl.gov

http://www.emsl.pnl.gov/

Jeff Ellison, PhD

Staff Scientist Inorganic Chemistry

EPIX Medical, Inc.

71 Rogers Street

Cambridgge, MA 02142-1118

USA

Ph: 617-250-6119

Fax: 617-250-6128

jellison@epixmed.com

Burt D. Ensley, PhD

CEO

NuCycle Therapy, Inc.

1 Deer Park Drive

Suite M

Monmouth Junction, NJ 8852

USA

Ph: 732 438 0900

Fax: 732 438 1209

burtensley@AOL.com

nucycletherapy.com

Daniel M. Epstein, PhD

Chemistry

SUNY Buffalo

POBox 3000

Buffalo, NY 14260-3000

USA

Ph: 215-321-1750

depstein@yahoo.com

Billy Joe Evans, PhD\*

Professor of Chemistry

Department of Chemistry

University of Michigan

930 N. University Avenue

Ann Arbor, MI 48109-1055

USA

Ph: 734/763-4228

Fax:

bjemag@umich.edu

Greg L. Evans, PhD

Program Administrator

Blood Diseases Program

NHLBI

6701 Rockledge Dr MSC 7950

Bethesda, MD 20892-7950

USA

Ph: 301-435-0055

Fax: 301-480-0868

evansg@nih.gov

Marguerite A. Evans\*

Program Officer

Division of Extramural Research, Training,& Review

National Center for Comp. and Alternative Medicine

31 Center Drive

Building 31, Room 5B58

Bethesda, MD 20892

USA

Ph: 301-402-5860

Fax: 301-402-4741

evansm@od.nih.gov

Dan Fabris

University of MD

Dept. of Chemistry and Biochemistry

1000 Hilltop Circle

Balitmore, MD 21250

USA

Ph: 410 455-3053

Fax: 410 455-2608

fabris@umbc.edu

www.umbc.edu

Ramy S. Farid, PhD\*

Assistant Professor

Department of Chemistry

Rutgers University

73 Warren St.

Newark, NJ 7102

USA

Ph: (973) 353-1254

Fax: (973) 353-1264

rfarid@newark.rutgers.edu

http://newark.rutgers.edu/\~rfarid

Nicholas P. Farrell, PhD

Professor of Chemistry

Virginia Commonwealth University

1001 West Main Street

PO Box 84-2006

Richmond, VA 23284-2006

USA

Ph: (804) 828-6320

Fax: (804) 828-8599

nfarrell@saturn.vcu.edu

Walt Fast, PhD

Postdoctoral Fellow

Chemistry

The Pennsylvania State University

152 Davey Laboratory

University Park, PA 16802

USA

Ph: 814-863-7965

Fax:

walt@chem.psu.edu

http://homes.chem.psu.edu/walt

Flavia Fedeles

Undergraduate student

Connecticut College

270 Mohegan Avenue

Box \# 3564

New London, CT 6321

USA

Ph: 860-439-3265

Fax: 860-439-2477

ffed@conncoll.edu

Paula F. Flicker, PhD

Program Director

Cell Biology and Biophysics

NIGMS

Bldg. 45, Rm 2AS.13H

45 Center Drive MSC 6200

Bethesda, MD 20892

USA

Ph: 301-594-3828

Fax: 301-480-2004

flickerp@nigms.nih.gov

Klaus Flix\*

National Cancer Institute

National Institutes of Health

Bethesda, MD 20892

USA

Bill R. Foster, MD\*

Senior Staff Physician

OD/OSPPA

NIH/NIDDK

Bldg.31, Rm 9A21

NIH

Bethesda, MD 20892

USA

Ph: 301-435-2991

Fax: 301-496-2830

fosterb@hq.niddk.nih.gov

Bruce A. Fowler, PhD\*

Director, Program in Toxicology

Toxicology

University of Maryland

1450 South Rolling Road

Baltimore, MD 21227

USA

Ph: (410) 455-6311

Fax: (410) 455-6314

bfowler@umbc.edu or drtox@earthlink.net

Elizabeth Fox, MD\*

Pediatric Oncology Branch

NCI

10/13N240

10 Center Dr.

Bethesda, MD 20892

USA

Ph: 301-496-1756

Fax: 301-402-0575

foxb@mail.nih.gov

Lynn Francesconi\*

USA

lfrances@hejira.hunter.cuny.edu

Kathy Franz, PhD

Postdoctoral Fellow

Chemistry

Massachusetts Institute of Technology

18-224

77 Massachusetts Ave

Cambridge, MA 2139

USA

Ph: 617 225-8605

Fax:

kfranz@mit.edu

Cathleen J. Frederickson

President

921 Sealy & Smith Bldg.

NeuroBioTex, Inc

200 University Blvd.

Galveston, TX 77550

USA

Ph: 409-762-0678

Fax: 413-825-0283

catfrederickson@hotmail.com

Christopher J. Frederickson, PhD

Professor

Anatomy & Neuroscience, Biomedical Engineering

University of Texas Medical Branch

625 Jennie Sealy Hospital

Mail Route 0456

University of Texas Medical Branch

Galveston, TX 77550-0456

USA

Ph: 409-762-0678

Fax: 413-825-0283

cjfreder@utmb.edu

www.brainzinc.com

Simon P Fricker, PhD\*

Director of Biology

AnorMED Inc

#200 20353 64th Avenue

Langley, BC V2Y 1N5

Canad

Ph: 604 5324653

Fax: 605 530 0976

sfricker@anormed.com

Fred K. Friedman, PhD

Principal Investigator

Laboratory of Metabolism

NCI

Bldg 37 Room 3E24

Bethesda, MD 20892

USA

Ph: 301-496-6365

Fax: 301-496-8419

fkfried@helix.nih.gov

Paul R. Gardner, PhD

Research Assistant Professor

Critical Care Medicine

Children\'s Hospital Research Foundation

3333 Burnet Ave.

Cincinnati, OH 45229

USA

Ph: 513-636-4885

Fax: 513-636-4892

gardp0@chmcc.org

http://www.cincinnatichildrens.org/FacultyandStaff

Mamta Gautam-Basak, PhD

Chemist

Division of Dermatology and Dental Drug Products

FDA

HFD-540

9201 Corporate Blvd.

Rockville, MD 20850

USA

Ph: 301-827-2074

Fax: 301-827-2091

gautambasakm@cder.fda.gov

Andrew Gelasco, PhD\*

Assistant Professor

Nephrology

Medical University of South Carolina

829 Clinical Science Bldg

96 Johnathan Lucas St

Charleston, SC 29425

USA

Ph: 843-577-5011

Fax: 843-953-6606

gelascoa@musc.edu

Zeke Gluzband\*

National Institutes of Health

National Institute of Aging

5600 Nathan Shock Drive

Baltimore, MD 21224-6825

USA

Ph: 410-558-8691

Fax: 410-558-8150

Hilary Arnold Godwin, PhD

Assistant Professor

Department of Chemistry

Northwestern University

2145 Sheridan Road

Department of Chemistry

Northwestern University

Evanston, IL 60208-3113

USA

Ph: (847) 467-3543

Fax: (847) 491-7713

h-godwin@nwu.edu

David Goldberg

Johns Hopkins University

Department of Chemistry

3400 N. Charles Street

Baltimore, MD 21218

USA

Ph: 410-516-7464

Fax: 410-516-8420

dpg@jhu.edu

Radoslav Goldman, PhD

Research Instructor

Lombardi Cancer Center

Georgetown University

NRB Rm W309

3970 Reservoir Rd

Washindton, DC 20007

USA

Ph: 202-6879868

rg26@gunet.georgetown.edu

Adoracion Gomez-Quiroga, PhD

Research Associate

Chemistry

Virginia Commonwealth University

P.O. Box 842006

1001 West Main Street

Richmond, VA 23284

USA

Ph: (804)828-0276

Fax: (804)828-8599

agomezqu@saturn.vcu.edu

Greg Goodman

National Cancer Institute

USA

Ph: 301 496-4932

Kathryn B. Grant, PhD

Assistant Professor of Biochemistry

Department of Chemistry

Georgia State University

University Plaza

Atlanta, GA 30303

USA

Ph: 404-651-0613

Fax: 404-651-1416

kbgrant@gsu.edu

Michael Guttman\*

Staff Scientist

LCE

NHLBI

10 Center Drive

Building 10, Room B1D416

Bethesda, MD 20892

USA

Ph: 301-496-1193

Fax: 301-402-2389

mguttman@nih.gov

Kamal E Habib, MD\*

Fellow

Clinical Neuroendocrinology

NIH

NIH Bldg 10, Rm 2D-46

Bethesda, MD 20892

USA

Ph: 301-496-8928

Fax: 301-402-1561

habib@codon.nih.gov

Trevor W Hambley, PhD

Associate Professor

School of Chemistry

University of Sydney

School of Chemistry

University of Sydney

NSW 2006, Australia

Sydney, NS 2006

Austr

Ph: 61-2-9351-2830

Fax: 61-2-9351-3329

t.hambley@chem.usyd.edu.au

Ingeborg Hanbauer

National Heart, Lung, and Blood Institute

James M Harnly, PhD

Research Leader

Food Composition Laboratory

USDA

Building 161, BARC-East

Beltsville, MD 20705

USA

Ph: 301-504-8356

Fax: 301-504-8314

harnly@bhnrc.usda.gov

Wesley R Harris, PhD

Professor of Chemistry

Chemistry

University of Missouri-St. Louis

8001 Natural Bridge Road

St. Louis, MO 63121

USA

Ph: (314) 516-5331

Fax: (314) 516-5342

wharris@umsl.edu

Earl H. Harrison, PhD\*

Research Chemist

Human Nutrition Research Center

USDA-Agricultural Research Service

BLD 308 Rm 101 BARC-East

Beltsville, MD 20705

USA

Ph: 301-504-7365

Fax: 301-504-9098

harrisone@bhnrc.arsusda.gov

Roger Haugwitz, PhD

Medicinal Chemist

Developmental Therapeutics Program

National Cancer Institute

Executive Plaza North, Suite 831

6130 Executive Boulevard MSC 7448

Bethesda, MD 20892-7448

USA

Ph: 301-496-8795

Fax: 301-480-4817

haugwitr@exchange.nih.gov

Alexander Hegmans, PhD

Research Associate

Chemistry

Virginia Commonwealth University

P.O. Box 842006

1001 West Main Street

Richmond, VA 23284

USA

Ph: (804)828-0276

Fax: (804)828-8599

ahegmans@saturn.vcu.edu

Craig L. Hill, PhD

Goodrich C. White Professor

Department of Chemistry

Emory University

Department of Chemistry

Atlanta, GA 30322

USA

Ph: (404) 727-6611

Fax: (404) 727-6076

chill@emory.edu

Shuk-mei Ho, PhD

University of Massachusetts Medical School

55 Lake Avenue North

Room S4-746

Worcester, MA 01655

USA

Ph: 508 856-1909

Fax: 508-856-8699

sally.krikorian@umassmed.edu

Vincent B. Ho, MD\*

Staff Radiologist

Diagnostic Radiology

NIH Clincal Center

Bldg. 10/Rm 1C660

10 Center Drive

Bethesda, MD 20892

USA

Ph: (301) 295-1898

Fax: (301) 295-2271

vho@nih.gov

Richard C. Holz, PhD

Associate Professor

Chemistry and Biochemistry

Utah State University

311 Maeser Laboratory

Logan, UT 84322

USA

Ph: (435)797-2609

Fax: (435)797-3390

Rholz@cc.usu.edu

http://www.chem.usu.edu/faculty/rholz/

Jiang Hong, MD PhD\*

Visiting Fellow

NIDDK

MCEB

1001Rockville pike Apt.515

Rockville, MD 20852

USA

Ph: 301-435-5638

Fax:

hong_jiang@hotmail.com

Maureen N. Hood

Research Coordinator

Diagnostic Radiology

Warren G Magnuson Clinical Center

Building 10, 1C660

9000 Rockville Pike

Bethesda, MD 20892

USA

Ph: (301) 319-6964

Fax: (301) 295-2271

mhood@usuhs.mil

Li-Shan Hsieh, PhD\*

Chemist

Division of Oncology Drug Products, FDA

1451 Rockville Pike

Rockville, MD 20857

USA

Ph: 301-594-0497

Fax: 301-594-0498

Hsiehl@cder.fda.gov

Hua-Fen Hsu, PhD

Postdoctoral Fellow

Chemistry

University of Minnesota

207 Pleasant Street SE

Minneapolis, MN 55455

USA

Ph: (612)6248874

Fax: (612)6242029

hsu@chem.umn.edu

Victor W. Huang\*

Graduate student

Biochemistry and Molecular Biology

University of Chicago

920 E. 58th St.

Chicago, IL 60637

USA

Ph: (773) 702-1667

vhuang@midway.uchicago.edu

Kristi J. Humphreys,

Graduate Student

Department of Chemistry

Johns Hopkins University

Remsen Hall

3400 N. Charles Street

Baltimore, MD 21218-2685

USA

Ph: 410-516-6557

Fax: 410-516-8420

kjh@jhunix.hcf.jhu.edu

Jeffrey H. Hurst, PhD

Health Scientist Administrator

National Heart, Lung and Blood Institute

Two Rockledge Center, Suite 7208

6701 Rockledge Drive

Bethesda, Md 20892-7924

USA

Ph: 301-435-0303

Fax: 301-480-3541

hurstj@nih.gov

Richard A. Ikeda, PhD

Program Director

Pharm., Physiol., and Biol. Chem.

National Institute of General Medical Sciences

Building 45, Room 2AS43B

45 Center Drive

Bethesda, MD 20892-6200

USA

Ph: 301-594-5938

Fax: 301-480-2802

ikedar@nigms.nih.gov

Olga Iranzo, PhD, MD

Chemistry

State University of New York at Buffalo

NSMC Box 603000

SUNY at Buffalo

Buffalo, NY 14260-3000

USA

Ph: (716)-645-6800

Fax: (716)-645-6963

iranzo@acsu.buffalo.edu

Hiroshi H Ishida, PhD

Research Scientist

Experimental Therapeutics

NCI

503 Robert Grant Avenue

Silver Spring, MD 20910

USA

Ph: 301-319-9621

Fax: 301-319-9449

hiroshi.ishida@na.amedd.army.mil

Paula Jacobs, PhD

Advanced Magnetics, Inc.

61 Mooney Street

Cambridge, MA 02138

USA

Ph: (617) 497-2070

Fax: (617) 546-2445

pjami@aol.com

Kenneth A. Jacobson, PhD\*

Chief, Molecular Recognition Section

Laboratory of Bioorganic Chemistry

Nat Inst Diabetes, Digestive, and Kidney Diseases

Bldg 8A, Rm B1A-17

8 Center Drive, MSC 0810

Bethesda, MD 20892

USA

Ph: 301-496-9024

Fax: 301-480-8422

kajacobs@helix.nih.gov

David Jacobus

President

Jacobus Pharmaceutical Company

P.O. Box 5290

Princeton, NJ 8540

Ph: 609-921-7447

Fax: 609-799-1176

dpjacobus@aol.com

Laran T. Jensen, PhD\*

Johns Hopkins University

615 N. Wolfe St. Rm 7032

Baltimore, MD 21205

USA

ljensen@jhsph.edu

Yichun Jian, PhD

Postdoctoral

NCI

41 Library Blvd.

Bethesda, MD 20892

USA

Gao Jin\*

Chinese Academy of Sciences

Life Sci R & D Center

Beijing, PR 100101

China

Ph: 86-10-6488587

Fax: 86-10-64854171

jgao@sun5.ibp.ac.cn

Lu Jingfen\*

Beijing Medical University

National Key Lab of Natural and Biomimetic Drugs

Beijing, China

62-091-517

62-015584

zdsljf@mail.bjmu.edu.cn

Jill I Johnson

Special Assistant to the Associate Director, DTP

Division of Cancer Treatment and Diagnosis

National Cancer Institute

Developmental Therapeutics Program

Bethesda, MD 20892

USA

Ph: (301) 435-9152

Fax: (301) 480-4817

johnsoji@mail.nih.gov

Sandra D. Jones

Clinical Research Nurse

Imaging Sciences Program, Diagnostic Radiology

Clinical Center

National Institutes of Health, Clinical Center

Building #10, Room 1C660

Bethesda, MD 20892

USA

Ph: (301) 496-7700

Fax: (301) 496-9933

sjones@cc.nih.gov

Chu W. Jung, PhD

Scientist

VPE Scientific

21 Coolidge Road

Arlington, MA 02476-7736

USA

Ph: 781-643-7868

Fax: 781-643-7868

drcjung@yahoo.com

Igor A Kaltashov, PhD

Assistant Professor

Chemistry

University of Massachusetts

Lederle Graduate Research Tower #701

Amherst, MA 1035

USA

Ph: (413)545-1460

Fax: (413)545-4490

kaltashov@chem.umass.edu

http://www.chem.umass.edu/kaltashov/kaltashov.html

Mijeong Kang

Graduate Student

Chemistry

Texas A&M University

Texas A&M University, chemistry department

P.O Box 30012

College station, TX 77842-3012

USA

Ph: 979-845-1966

Fax: 979-845-7177

kang@mail.chem.tamu.edu

Kenneth D. Karlin, PhD

Professor of Chemistry

Department of Chemistry

Johns Hopkins University

Remsen Hall

3400 N. Charles Street

Baltimore, MD 21218-2685

USA

Ph: 410-516-8027

Fax: 410-516-8420

karlin@jhuvms.hcf.jhu.edu

http://jhunix.hcf.jhu.edu/\~karlin/

John V. Kelsey

Dental Team Leader

Division of Dermatologic and Dental Drug Products

Food and Drug Administration

HFD-540; Rm N258

Rockville, MD 20850

USA

Ph: 301.827.2068

Fax: 301.827.2075

kelseyj@cder.fda.gov

Salma Kiani, PhD

Research Fellow

Radiology

Children\'s Hospital/Harvard Medical School

Division of Nuclear Medicine

Children\'s Hospital

300 Longwood Ave

Boston, MA 2115

USA

Ph: 617-3557560

Fax: 617-2320517

kiani@hub.tch.harvard.edu

Young S. Kim, PhD\*

Special Expert

Nutritional Sciences Research Group

NCI

6130 Executive Blvd.,EPN 212C

Rockville, MD 20858

USA

Ph: 301-496-8573

Fax: 301-402-0553

yk47s@nih.gov

Stephen Koch

Stony Brook University

USA

Ph: 613-632-7944

John W. Kozarich, PhD

Vice President of Biochemistry

Merck Research Labs, RY 80 M-101

Merck & Company

PO Box 2000

Rahway, NJ 07065-0900

USA

Ph: (732) 594-3249

Fax: (732) 594-3695

john_kozarich@merck.com

Morris Krauss, PhD

Senior Fellow

Center Advanced Research Biotechnology

National Institute Standards Technology

9600 Gudelsky Drive

Rockville, MD 20850

USA

Ph: 3017386242

Fax: 3017386255

krauss@octank.carb.nist.gov

www.carb.nist.gov

Bala S Krishnan, PhD\*

Sr. Principal Scientist

Discovery Analytical Sciences

Bristol-Myers Squibb company

5 Research Parkway

Wallingford, CT 6492

USA

Ph: (203) 677 6343

Fax: (203) 677 7702

krishnab@bms.com

Don Kupp\*

Powder Processing Technologies

501 Wyoming Road

Newark, DE 19716

USA

Ph: (302) 369-6757

Fax: (302) 369-6763

dkupp@fraunhofer.org

Karen A Kurdziel, MD\*

Research Fellow

Imaging Sciences

National Institutes of Health

10 Center Drive

Bldg 10

1C401/mail stop 1C497

Bethesda, MD 20892

USA

Ph: 3014352155

Fax: 3014960114

kkurdziel@mail.cc.nih.gov

Joseph W. Lam, PhD

Research Officer

Institute of National Measurement Standards

National Research Council of Canada

Chemical Metrology Group

Building M-12

Montreal Road

Ottawa, On K1A 0R6

Can

Ph: (613) 998-8380

Fax: (613) 993-2451

joe.lam@nrc.ca

Robin C. Lasey

Graduate Student

Dept. of Chem. and Center for Photochemical Sci.

Bowling Green State University

Department of Chemistry

Bowling Green, OH 43402

USA

Ph: 419-372-8520

Fax: 419-372-9809

rlasey@bgnet.bgsu.edu

Randall B. Lauffer, PhD

Chief Scientific Officer

EPIX Medical, Inc.

71 Rogers Street

Cambridge, MA 02142-1118

USA

Ph: (617) 499-1401

Fax: (617) 499-1415

rlauffer@epixmed.com

Catherine Law\*

National Cancer Institute

USA

Neil A. Law, PhD

Michigan State University

Department of Chemistry

Michigan Univ

East Lansing, MI 48824-1322

USA

Ph: 517-355-9715

Fax: 517-353-1793

law@photon.cem.msu.edu

Hong In Lee, PhD

Research Fellow

Laboratory of Biochemistry

NHLBI, NIH

Building 3, Room 216

3 Center Drive

Bethesda, MD 20892

USA

Ph: 301-435-2354

Fax: 301-496-0599

leehi@nhlbi.nih.gov

Kan Sam Lee, PhD

NIH/CBDB

10 Center Drive

BLDG 10, Rm 3C208

Bethesda, MD 20892

USA

Ph: 301-435-6383

Fax: 301-480-2322

leek@intra.nimh.nih.gov

Peter Leopold, PhD\*

Vice President

ProteiGene Inc.

236 Concord Ave.

Cambridge, MA 2138

USA

Ph: 617-491-6297

Fax: 617-868-9807

pel@proteigene.com

www.proteigene.com

Cathy W Levenson, PhD\*

Associate Professor

Program in Neuroscience

Florida State University

Florida State University

237 Biomedical Research Facility

Tallahassee, FL 32306-4340

USA

Ph: 850-644-4122

Fax: 850-644-0989

levenson@neuro.fsu.edu

www.neuro.fsu.edu

Rod Levine, MD PhD

Section Chief

Laboratory of Biochemistry

NIH, NHLBI

Bldg 3, Room 106

MSC 0320

Bethesda, MD 20892-0320

USA

Ph: 301 496-2310

Fax: 301 496-0599

rlevine@nih.gov

Catherine D. Lewis, PhD

Branch Chief

CBB

CBB, NIGMS, NIH

45 Center Dr.

Bethesda, MD 20894

USA

Ph: 301-594-0828

Fax: 301-480-2004

lewisc@nigms.nih.gov

Jason S. Lewis, PhD

Research Associate

Radiological Sciences

Washington University School of Medicine

510 South Kingshighway Blvd

Campus Box 8225

Saint Louis, MO 63110

USA

Ph: 314-362-4696

Fax: 314-362-9940

lewisjas@mir.wustl.edu

Marilyn M. Lightfoote, PhD MD

Director, Division of Life Sciences

Food and Drug Administration

Office of Science and Technology, CDRH/FDA

12709 Twinbrook Parkway

Rockville, MD 20852

USA

Ph: 301-443-7115

Fax: 301-594-6775

mml@cdrh.fda.gov

Stephen J. Lippard, PhD

Arthur Amos Noyes Professor & Chai

Department of Chemistry

Massachusetts Institute of Technology

77 Massachusetts Avenue, Rm 18-590

Cambridge, MA 02139-4307

USA

Ph: (617) 253-1892

Fax: (617) 258-8150

lippard@lippard.mit.edu

Jie Liu, PhD MD

NCI at NIEHS

Inorganic Carcinogenesis Section

111 Alenxander Drive

Mail Drop F0-09, Room F-017

NCI at NIEHS/NIH

Research Triangle Park, NC 27709

USA

Ph: 919-541-3951

Fax: 919-541-3970

liu6@niehs.nih.gov

Shuang Liu, PhD

Principal Research Chemist

Medical Imaging Division

Dupont Pharmaceuticals Company

331 Treble Cove Road

North Billerica, MA 1862

USA

Ph: (978) 671-8696

Fax: (978) 436-7500

shuang.liu@dupontpharma.com

Yi Lu, PhD

Assistant Professor of Chemistry

Chemistry

University of Illinois at Urbana-Champaign

600 S. Mathews Avenue, MC-712

Box 8-6

Urbana, IL 61801

USA

Ph: 217-333-2619

Fax: 217-333-2685

yi-lu@uiuc.edu

http://www.scs.uiuc.edu/chem/lu.htm

Roger Luo, PhD

Visiting Research Fellow

NCI

NIH

Bldg 10, B3B69

10 Center Dr.

Bethesda, MD 20892

USA

Ph: 301 496-6027

Fax: 301 402-1923

luor@pop.nci.nih.gov

Elise T Luong, PhD\*

Mass Spectroscopist

NHGRI

NIH

9 Memorial Drive, Room 1W123, MSC 0955

Bethesda, MD 20892

USA

Ph: 301-402-3899

Fax: 301-480-9667

eluong@nhgri.nih.gov

Svetlana Lutsenko, PhD

Assistant Professor

Biochemistry and Molecular Biology

Oregon Health Sciences University

3181 SW Sam Jackson Park Road

L224

Portland, OR 97201

USA

Ph: 503-494-6953

Fax: 503-494-8393

lutsenko@ohsu.edu

Erin S. F. Ma, PhD

Research Associate

Chemistry

Virginia Commonwealth University

P.O. Box 842006

1001 West Main Street

Richmond, VA 23284

USA

Ph: (804)828-0276

Fax: (804)828-8599

esma@saturn.vcu.edu

Sanku Mallik, PhD\*

Assistant Professor

Chemistry

North Dakota State University

Ladd Hall

Fargo, ND 58105

USA

Ph: 701-231-8829

Fax: 701-231-8831

sanku_mallik@ndsu.nodak.edu

Rajesh Manchanda, PhD\*

Associate Director, Scientific Affairs

Diatide, Inc.

9 Delta Drive

Londonderry, NH 3053

USA

Ph: (603) 437-8970

Fax: (603) 437-8977

r_manchanda@diatide.com

Wolfgang Maret, PhD

Assistant Professor

Center for Biochemical and Biophysical Sciences

Harvard Medical School

250 Longwood Ave

S.G. Mudd Bldg, 1st floor

Boston, MA 2115

USA

Ph: 617-432-5685

Fax: 617-566-3137

wolfgang_maret@hms.harvard.edu

Rosemary Marusak

Kenyon College

Dept of Chemistry

Gambier, OH 43022

USA

marusakr@kenyon.edu

Luigi G. Marzilli, PhD\*

Professor

Department of Chemistry

Emory University

1515 Pierce Drive

Atlanta, GA 30322

USA

Ph: 404-727-6603

Fax: 404-727-6586

lmarzil@emory.edu

John H. McNeill, PhD\*

Professor

Division of Pharmacology & Toxicology

The University of British Columbia

Faculty of Pharmaceutical Sciences

2146 East Mall

Vancouver, BC V6T 1Z3

Canada

Ph: (604) 822-9373

Fax: (604) 822-8001

jmcneill@unixg.ubc.ca

http://www.ubcpharmacy.org/mcneill.htm

Thomas J. Meade, PhD

Bechman Institute 139-74

California Institute of Technology

Bechman Institute

Pasadena, CA 91125

USA

Ph: (626) 395-2776

Fax: (626) 449-5163

tmeade@gg.caltech.edu

Claude F. Meares, PhD

Professor

Chemistry

University of California

Room 190A Chemistry

One Shields Avenue

Davis, CA 95616-5295

USA

Ph: 530-752-0936

Fax: 530-752-8938

cfmeares@ucdavis.edu

http://www-chem.ucdavis.edu/people/meares.html

John Melograna

Regulatory Toxicologist

Division of Medical Imaging

FDA

5600 Fishers Lane, HFD-160

Rockville, MD 20857

USA

Ph: 301-827-7503

Fax: 301-480-6036

jm999999999@yahoo.com

Anne E. Menkens, PhD

Program Director

NCI

EPN 800

6130 Executive Blvd.

Rockville, MD 20852

USA

Ph: 301-496-9531

Fax: 301-480-5785

am187k@nih.gov

Kenneth M. Merz, Jr., PhD

Professor

Department of chemistry

Pennsylvania State University

152 Davey Lab

University Park, PA 16802-2801

USA

Ph: (814) 865-3623

Fax: (814) 863-8403

merz@psu.edu

Timothy A. Mietzner, PhD\*

University of Pittsburgh School of Medicine

Department of Molecular Genetics and Biochemistry

BST E1240

Pittsburgh, PA 15261

USA

Ph: (412) 648-9244

mietzner+@pitt.edu

Yuji Mikata, MD

Postdoctral Fellow

Chemistry

MIT

Room 18-528, Massachusetts Institute of Technology

Cambridge, MA 02139-4307

USA

Ph: 617-253-1824

Fax: 617-258-8150

mikata@lippard.mit.edu

Michelle Millar

SUNY at Stonybrook

USA

Ph: 613-632-7909

Richard A. Miller, MD

President and Chief Executive Officer

Pharmacyclics

995 E. Arques Ave

Sunnyvale, CA 94086-4521

USA

Ph: (408) 774-0330

Fax: (408) 774-0340

rmiller@pcyc.com

Nancy J. Miller-Ihli, PhD\*

Research Chemist

Food Composition Lab

USDA

Rm. 1 Bldg. 161 BARC-East

Beltsville, MD 20705

USA

Ph: 301-504-8252

Fax: 301-504-8314

miller-ihli@bhnrc.usda.gov

John A. Milner, PhD\*

Acting Chief

Division Cancer Prevention, NCI

Nutritional Science Research Group

Executive Plaza North Suite 212

6130 Executive Blvd.

Rockville, MD 20852

USA

Ph: 301=496-0118

Fax: 301-402-0553

milnerj@mail.nih.gov

Jeff Moore, PhD\*

President

Phylogix LLC

69 U.S. Route One

P.O. Box 6790

Scarborough, ME 4070

USA

Ph:

Fax:

jmoore@phylogix.com

Doug Morris, PhD

Staff Scientist

NHLBI / LCE

NIH

10 Center Dr.

Bldg 10, Rm B1D-416

Bethesda, MD 20892

USA

Ph: 301-435-5859

Fax: 301-402-2389

dmorris@nih.gov

Janet R. Morrow, PhD

Associate Professor of Chemistry and Medicinal Chemistry

Chemistry

State University of New York at Buffalo

526 Natural Sciences and Mathematics Complex

Amherst, NY 14221

USA

Ph: 716-645-6800

Fax: 716-645-6963

jmorrow@acsu.buffalo.edu

Sarah Nahmia

Princeton Univerisity

USA

David B. Newlin, PhD\*

Research Psychologist

NIH \-- NIDA \-- Intramural

5500 Nathan Shock Dr.

Baltimore, MD 21224

USA

Ph: (410) 550-1411

Fax: (410) 550-1633

dnewlin@intra.nida.nih.gov

Ronald E. Noftle, PhD

Professor of Chemistry

Chemistry

Wake Forest University

Box 7486

Wake Forest University

Winston-Salem, NC 27109

USA

Ph: 336-758-5520

Fax: 336-758-4656

noftle@wuf.edu

Nnenna Uchechi Nwokekeh\*

pre-IRTA

LBG

NIDDK

Bldg 8 Rm 2A02

Bethesda, MD 20892

USA

Ph: 301-594-5257

Fax: 301-402-0240

nn40b@nih.gov

Kevin John O\'Brien\*

Nurse Practitioner

Pediatrics and Developmental Neuropsychiatry

NIMH

Bldg 10 Clinical Center

Rm 4N208

Bethesda, MD 20892

USA

Ph: 301-402-8468

Fax: 301-402-8497

obrien@codon.nih.gov

Robert W. Odom, PhD

Senior Scientist and Manager, Analytical Contracts

Charles Evans & Associates

301 Chesapeake Drive

Redwood City, CA 94063

USA

Ph: 650-369-3867

Fax: 650-369-7921

rodom@cea.com

Michael Ogawa, PhD

Associate Professor

Center for Photochemical Sciences

Bowling Green State University

Department of Chemistry

Bowling Green, OH 43403

USA

Ph: (419) 372-2809

Fax: (419) 372-9809

mogawa@bgnet.bgsu.edu

http://www.bgsu.edu/departments/photochem/ogawa.html

Thomas V. O\'Halloran, PhD

Professor

Department of Chemistry

Northwestern University

2145 Sheridan Road

Evanston, IL 60208-3113

USA

Ph: (847) 491-5060

Fax: (847) 491-7713

t-ohalloran@nwu.edu

Stanley J. Opella\*

University of Pennyslvania

Department of Chemistry

231 S. 34th Street

Philadelphia, PA 19104

USA

Ph: (215) 898-6459

Fax: (215) 573-2123

opella@sas.upenn.edu

Chris Orvig, PhD

Professor of Chemistry and Pharmaceutical Sciences

Department of Chemistry

University of British Columbia

2036 Main Mall

Vancouver, BC V6T 1Z1

Canada

Ph: (604) 822-4449

Fax: (604) 822-2847

orvig@chem.ubc.ca

http://www.chem.ubc.ca/faculty/orvig/

Alan B. Packard, MD

Sr. Research Associate/Asst. Professor

Nuclear Medicine

Children\'s Hospital/Harvard Medical School

300 Longwood Ave.

Boston, MA 2115

USA

Ph: 617-355-7539

Fax: 617-232-0517

packard@a1.tch.harvard.edu

Shrikant Pagay,

Chemist

DHHS/FDA/CDER/OPS/DNDCIII

Food and Drug Administration

Corporate Bldg 2, Rm N329

Mail Stop HFD-520

9201 Corporate Blvd

Rockville, MD 20850

USA

Ph: 301-827-2179

Fax: 301-827-2327

pagays@cder.fda.gov

Vinay M Pai, PhD\*

Research Fellow

National Heart, Lung and Blood Institute

National Institutes of Health

Laboratory of Cardiac Energetics

Bldg. 10, Room B1D-523, MSC 1061

Bethesda, MD 20892-1061

USA

Ph: 3014962992

Fax: 3014022389

vp53y@nih.gov

http://zeus.nhlbi.nih.gov/\~paiv/

Sanjay K. Pandey, PhD

Visiting Fellow

Diabetes Section

NIH/NIA

GRC, LCI

5600 Nathan Shock Drive, Box 23

Baltimore, MD 21224-2780

USA

Ph: (410) 558-8410

Fax: (410) 558-8381

pandeys@grc.nia.nih.gov

Irina V. Panyutin, MD\*

Staff scientist

NMD

NIH/CC

NIH, bld.10,CC/NMD,1C401, 10 Central Dr.

Bethesda, MD 20892

USA

Ph: 301-4027403

Fax: 301-4809712

irina@nmdpet.cc.nih.gov

Igor Panyutin, PhD

Staff Scientist

Nuclear Medicine

NIH

10 center Dr

Rm 10/1C401

Bethesda, MD 20892

USA

Ph: 301-496-8308

Fax: 301-480-9712

igorp@helix.nih.gov

Dierdre A Pearce, PhD

Postdoctoral

Department of Chemistry

Massachusetts Institute of Technology

18-224

77 Massachusetts Avenue

Cambridge, MA 2139

USA

Ph: 617 253 0206

Fax: 617 452 2419

dierdre@mit.edu

Linda L. Pearce\*

University of Pittsburgh School of Medicine

Dept of Pharmacology

200 Lothrop Street

Pittsburgh, PA 15261

USA

Ph: (412) 648-2057

lip10+@pitt.edu

Michael L. Pendrak, PhD

CRTA

Laboratoryof Pathology

NCI

10 Center Drive

Room 2A23

Bethesda, MD 20892

USA

Ph: 301-496-6264

Fax: 301-402-0043

mpendrak@helix.nih.gov

David H. Petering, PhD

Professor of Chemistry

Chemistry

University of Wisconsin-Milwaukee

Department of Chemistry

University of Wisconsin-Milwaukee

Milwaukee, WI 53201

USA

Ph: 414-229-5853

Fax: 414-229-5530

petering@uwm.edu

Abbas Pezeshk, PhD\*

Professor and Chair

Chemistry

Moorhead State University

7th Avenue and 11 street

Moorhead, MN 56563

USA

Ph: 218-236-2257

Fax: 218-236-2999

pezeshk@mnstate.edu

Mary Frances A. Picciano

Visiting Nutritionist

NIH

Office of Dietary Supplements

31 Center Drive

1B29

Bethesda, MD 20892

USA

Ph: 301-435-3607

Fax: 301-480-1845

piccianm@od.nih.gov

Bruce Pitt\*

University of Pittsburgh School of Medicine

Dept of Pharmacology

200 Lothrop Street

Pittsburgh, PA 15261

USA

\(412\) 648-2056

Brucep+@pitt.edu

David Piwnica-Worms, MD/PhD

Professor

Program in Bioorganic Chemistry

Washington University School of Medicine

Program in Bioorganic Chemistry

St. Louis, MO 63110

USA

Ph: (314) 362-9356

Fax: (314) 362-0152

piwnica-wormsd@mir.wustl.edu

David A. Place, PhD

Chemist

Center for Drug Evaluation Research

Food and Drug Administration

Parklawn Bldg, Rm 18B09

Mail Stop HFD-160

5600 Fishers Lane

Rockville, MD 20857

USA

Ph: (301) 827-7510

Fax: (301) 443-9281

placed@cder.fda.gov

Roy Planalp

University on New Hampshire

USA

Patricia A. Pleban, PhD\*

Associate Professor

Dept. Chemistry & Biochemistry

Old Dominion University

Alfriend Chemistry Bldg

Norfolk, VA 23529-0266

USA

Ph: (757) 683-4085

Fax: (757) 683-4628

ppleban@odu.edu

Thomas C. Pochapsky, PhD

Professor

Department of Chemistry

Brandeis University

MS15

Waltham, MA 02454-9110

USA

Ph: 781-736-2559

Fax: 781-736-2516

pochapsky@brandeis.edu

http://pochapsky.chem.brandeis.edu

Indra Poola, PhD

Howard University College of Medicine

Biochemistry and Molecular biology and Pharma

520 W. Street, NW

Washington, DC 20059

USA

poola@hucmphrm.howard.edu

Thomas L. Poulos, PhD

Professor

Department of Molecular Biology and Biochemistry

University of California-Irvine

Department of Molecular Biology and Biochemistry

Irvine, CA 92697-3900

USA

Ph: (949) 824-7020

Fax: (949) 824-3280

poulos@uci.edu

Peter C. Preusch, PhD

Program Director

Pharmacology, Physiology, and Biological Chemistry

National Institute of General Medical Sciences

45 Center Drive, MSC 6200

Bethesda, MD 20892-6200

USA

Ph: 301-594-5938

Fax: 301-480-2802

preuschp@nigms.nih.gov

Ann Przyborowska

University of New Hampshire

Parsons Hall #231

Durham, NH 03824-3598

USA

\(603\) 862-2511

aniusia5@hotmail.com

Steven Yue Qian, PhD

Visiting Fellow

LPC/NIEHS/NIH

P.O. Box 12233, MD F0-02

Res. Triangle Park, NC 27709

USA

Ph: (919) 541-0495

Fax: (919) 541-1043

qian1@niehs.nih.gov.

Stephen W. Ragsdale, PhD\*

Professor

Biochemistry

University of Nebraska

Beadle Center

Dept of Biochemistry

University of Nebraska

Lincoln, NE 68588-0664

USA

Ph: 402-472-2943

Fax: 402-472-7842

sragsdale1@unl.edu

http://www.pigment.unl.edu/dept/Ragsdale/homepage.html

Daniel J. Raiten, PhD\*

Health Scientist Administrator

Office of Prevention Research and Interntl Prog.

NIH/NICHD

6100 Executive Blvd

Bethesda, MD 20892

USA

Ph: (301)435-7568

Fax: (301)435-0009

raitend@mail.nih.gov

Martina Ralle, PhD

Research Scientist

BMB

Oregon Graduate Institute of Science and Technolog

20,000 N. W. Walker Rd

Beaverton, OR 97006

USA

Ph: 503-748-1217

Fax: 503-748-1217

ralle@bmb.ogi.edu

www.cbs.ogi.edu/\~ralle

Robert R. Rando\*

Harvard Medical School

Dept of Biological Chemistry and Molecular Pharma

250 Longwood Ave

Boston, MA 02115

USA

\(617\) 432-1794

\(617\) 432-0471

rando@hms.harvard.edu

Kenneth N. Raymond, PhD

Professor of Chemistry

Department of Chemistry

University of California

Department of Chemistry

University of California

Berkeley, CA 94720-1460

USA

Ph: 510-642-7219

Fax: 510-486-5283

raymond@socrates.berkeley.edu

http://www.cchem.berkeley.edu/\~knrgrp/home.html

Sakineh Redjali\*

Consultant

8513 Capo Court

Vienna, VA 22182

USA

Ph: 703-821-1220

Fax:

ksm@erols.com

Uwe Richter, MD

Guest Researcher

Biotechnology Division

National Institute of Standards and Technology

Center for Advanced Research in Biotechnology

9600 Gudelsky Drive, B107

Rockville, MD 20850

USA

Ph: 301 738 6133

Fax: 301 738 6255

uwe@nist.gov

Dennis P. Riley, PhD

Vice-President for Research & Development

Research and Development

MetaPhore Pharmaceuticals, Inc.

1910 Innerbelt Business Center Dr.

St. Louis, MO 63114

USA

Ph: (314) 426-4803

Fax: (314) 426-7491

dpriley@metaphore.com

Charles G. Riordan, PhD

Chemistry and Biochemistry

University of Delaware

Brown Laboratory

Newark, DE 19716

USA

Ph: 302-831-1073

Fax: 302-831-6335

riordan@udel.edu

www.udel.edu/chem/riordan

Rosette M. Roat, PhD

Adjunct Professor of Chemistry

Chemistry

Washington College

300 Washington Ave.

Chestertown, MD 21620

USA

Ph: 410-778-2800

Fax: 410-778-7275

roatmalone@hotmail.com

Kenton R. Rodgers, PhD

Associate Professor

Chemistry

North Dakota State University

Ladd Hall

Fargo, ND 58105-5516

USA

Ph: 701-231-8746

Fax: 701-231-8831

rodgers@plains.nodak.edu

Michael E. Rogers, PhD

Division Director

PPBC

NIGMS

45 Center Lane

Bethesda, VA 20892

USA

Ph: 301-594-3827

Fax: 301-480-2802

rogersm@nigms.nih.gov

Steve Rokita, PhD

Professor

Chemistry and Biochemistry

University of Maryland

Building 91

College Park, MD 20742

USA

Ph: 301-405-1816

Fax: 301-405-9376

sr101@umail.umd.edu

http://www.chem.umd.edu/organic/rokita/Rokita.html

Clifford S Rossiter

Graduate Student in Medicinal Chemistry

Department of Medicinal Chemistry

SUNY at Buffalo

197 Rounds Ave.

Upper Apt.

Buffalo, NY 14215

USA

Ph: 716-837-0362

<rossiter@acsu.buffalo.edu>

Tracey Roualt

NICHD

USA

Ph: 301 496-6368

Norka Ruiz Bravo, PhD

Associate Director for Extramural Activities, NIGMS

National Institute of General Medical Sciences

National Institutes of Health

45 Center Drive, Room 2AN24H

Bethesda, MD 20892

USA

Ph: 301-594-4499

Fax: 301-480-1852

ruizbran@nigms.nih.gov

Frank M. Rusnak, PhD

Assoc. Professor, Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

Mayo Clinic and Foundation

549 Plummer Building

200 SW First Street

Rochester, MN 55905

USA

Ph: 507-284-4743

Fax: 507-284-8286

rusnak@mayo.edu

http://www.mayo.edu/research/rusnak_lab/

Matthew Ryle\*

Michigan State University

Hausinger Lab

160 Giltner Hall

E. Lansing, MI 48824

USA

Ph: (517) 353-7295

Fax: (517) 353-8957

ryle@pilot.msu.edu

Omowunmi A. Sadik, PhD\*

Assistant Professor

Department Of Chemistry

State University Of New York At Binghamton

PO. Box 6016

E. Vestal Pkwy

Binghamton, NN 13902

USA

Ph: 607-777-4132

Fax: 607-777-4478

osadik@binghamton.edu

http://chemiris.chem.binghamton.edu:8080/SADIK/sadik.htm

Jose-Luis Sagripanti, PhD\*

Research Chemist

Molecular Biology Branch (HFZ-113)

Food and Drug Administration

12709 Twinbrook Parkway

Rockville, MD 20852

USA

Ph: (301) 443-7186

Fax:

jus@cdrh.fda.gov

Milagros Salazar, PhD

Food and Drug Adminstration

USA

Ph: 301 827-7493

Daniela Salvemini, PhD

Director of Biology

MetaPhore Pharmaceuticals

1910 Innerbelt Business Center Drive

St Louis, MO 63114

USA

Ph: 314 4126 4803

Fax: 314 426 7491

dsalvemini@metaphore.com

Meinrado Samala

University of MD

USA

Bibudhendra Sarkar

Head, Structural Biology and Biochemistry

Department of Structural Biology and Biochemistry

The Hospital for Sick Children

555 University Ave

Toronto, ON M5G-1X8

Canada

Ph: 416-813-5921

Fax: 416-813-5379

bsarkar@sickkids.on.ca

Elliott (NMI) Schiffmann, PhD

Scientist Emeritus

Lab. of Pathology

National Cancer Inst., NIH

9000 Rockville Pike

Bethesda, MD 20892

USA

Ph: 301 496 3324

Fax:

elliotts@box-e.nih.gov

Joel P Schneider, PhD\*

Assistant Professor of Chemistry and Biochemistry

Chemistry and Biochemistry

University of Delaware

Newark, DE 19716-2522

Newark, DE 19716-2522

USA

Ph: (302) 831 3024

Fax: (302) 831 6335

schneijp@udel.edu

Chad W. Schwietert, PhD\*

Dept. of Chemistry and Biochemistry

San Francisco State University

1600 Holloway Ave

San Francisco, CA 94132

USA

Ph: 650-871-8775

Fax: 650-871-8775

cschwiet@sfsu.edu

William T. Self, PhD\*

National Heart, Lung, and Blood Institute

USA

\(301\) 496-1315

Robert H. Selwitz, DDS, MPH

Senior Dental Epidemiologist

Office of Science Policy and Analysis

Nat\'l. Institute of Dental & Craniofacial Research

Natcher Building, Room 3AN-44

45 Center Drive MSC 6401

Bethesda, MD 20878-5238

USA

Ph: 301-594-3977

Fax: 301-435-8667

robert.selwitz@nih.gov

Mary Sexton, PhD\*

Professor

Department of Epidemiology

U Of Maryland School of Medicine

102 Howard Hall

650 W. Redwood Street

Baltimore, MD 21201

USA

Ph: (410) 706-3488

Fax: (410) 706-8013

msexton@som.umaryland.edu

Shubh Sharma, PhD

Edison Corporate Center

Palatin Technologies, Inc.

175 May St., Suite 500

Edison, NJ 8837

USA

Ph: (732) 225-3883

Fax: (732) 346-0779

smidas@aol.com

Rass M Shayiq, PhD\*

Scientific Review Administrator

NIH

Council for Scientific Research

MSC 7818, Room 2175

6701 Rockledge Drive

Bethesda, MD 20892

USA

Ph: 301-435-2359

Fax: 301-480-1171

shayiqr@csr.nih.gov

Jian Shen

Wayne State

USA

Arthur S. Sherman, PhD

Senior Investigator

MRB

NIDDK

9190 Rockville Pike Suite 350

Bethesda, MD 20892-2690

USA

Ph: 301-496-4325

Fax: 301-402-0535

asherman@nih.gov

http://mrb.niddk.nih.gov/sherman

B. Vithal Shetty

Chemist

DHHS/FDA/CDER/OPS/DNDCIII

Food and Drug Administration

Corporate Bldg 2, Rm N356

Mail Stop HFD-520

9201 Corporate Blvd

Rockville, MD 20850

USA

Ph: 301-827-2187

Fax: 301-827-2431

shetty@cder.fda.gov

Roman Shimanovich

Graduate Student

Department of Chemistry

Princeton University

Frick Chemical Laboratory

Princeton University

Washington Rd & William St

Princeton, NJ 8544

USA

Ph: 609-258-3449

Fax:

romans@princeton.edu

http://www.princeton.edu/\~jtggroup

Hisanori Shiomi, MD PhD\*

Postdoctoral Fellow

Laboratory of Experimental Carcinogenesis

NCI

Building 37 Room 3C28

37 Convent Drive MSC4255

Bethesda, MD 20892

USA

Ph: 301-496-5688

Fax: 301-496-0734

hisanori_shiomi@nih.gov

Dina M. Sigano, PhD

National Institutes of Health

National Cancer Institute

37 Convent Drive

Bldg 37 Room 5B15

Bethesda, MD 20892

USA

Urszula Slomczynska, PhD

Director of Chemistry

Research and Develpoment

MetaPhore Pharmaceuticals, Inc.

1910 Innerbelt Business Center Dr.

St. Louis, MO 63114

USA

Ph: 314 4264803

Fax: 314 4267491

uslomczynska@metaphore.com

Janet L Smart, PhD

VP

Corporate Development

Eukarion, Inc.

6F Alfred Circle

Bedford, MA 1730

USA

Ph: 781-275-0424

Fax: 781-275-0752

j.smart@eukarion.com

www.eukarion.com

Tatyana I Smirnova, PhD

Postdoctoral fellow

University of Illinois

506 S. Mathews

Urbana, IL 61801

USA

Ph: 217-244-2252

Fax: 217-333-8868

tsmirnov@uiuc.edu

Karn Sorasaenee

Graduate Assistant

Chemistry

Texas A&M University

Chemistry Department

Texas A&M University

P.O.Box 30012

College Station, TX 77842-3012

USA

Ph: 979-845-1966

Fax: 979-845-7177

Sorasaenee@mail.chem.tamu.edu

Ashok Srivastava, MD

Associate Professor of Medicine and Head Lab.Cell Signaling

Res. Center,CHUM-Hotel-Dieu

University of Montreal

3850 Rue Saint Urbain

Montreal, QC J4X-1W4

CANAD

Ph: 514-843-2917

Fax: 514-843-2911

ashok.srivastava@umontreal.ca

Ivan Stangel, MD\*

President & Director of Research

BioMat Sciences

9700 Great Seneca Highway

Rockville, MD 20850

USA

Ph: 240-453-6248

Fax: 240-453-6208

stangel

ulabran

Pamela E. Starke-Reed, PhD\*

Deputy Director

DNRC, NIDDK

NIH, Division of Nutrition Research Coordination

Rockledge 1, Suite 8048

6705 Rockledge Dr.

NIH

Bethesda, MD 20892

USA

Ph: 301 594 8805

Fax: 301 480 3768

PS39P@NIH.GOV

Theresa Staropoli

Laboratory Technician

Chemistry

Virginia Commomwealth University

P.O. Box 842006

1001 West Main Street

Richmond, VA 23284

USA

Ph: (804)828-0276

Fax: (804)828-8599

tstaropoli@netscape.net

Ethan Dane Sternberg

Research Associate

Chemistry

University of British Columbia

2036 Main Mall

Vancouver, BC V6T-1Z1

Canad

Ph: 604-822-3200

Fax: 604-822-2847

<ethan@chem.ubc.ca>

Barbar Stoecker

Olkomahma State University

USA

Ralph Edward Sturgeon, PhD

Senior Research Officer

Institute for National Measurement Standards

National Research Council

M12, G9

1500 Montreal Rd.

Ottawa, ON K1A-0R6

Can

Ph: (613) 993-6395

Fax: (613) 993-2451

ralph.sturgeon@nrc.ca

www.cm.inms.nrc.ca

Fan Su

University of NH

USA

R. Subramanian, PhD\*

Director, R&D

Best Medical International

7643 Fullerton Road

Springfield, VA 22153

USA

Ph: 703-451-2378

Fax: 703-451-4977

mannys@best-medical.com

Anne O. Sumers, PhD\*

Professor

Microbiology

The University of Georgia

527 Biological Sciences Building

Athens, GA 30602-2605

USA

Ph: 706-542-2669

Fax: 706-542-6140

summers@uga.edu

http://www.uga.edu/mib/aosummers.htm

Helen Sunshine, PhD

Chief, Office of Scientific Review

Office of Scientific Review

National Institute of General Medical Sciences

National Institutes of Health

45 Center Drive, MSC 6200

Bethesda, MD 20892-6200

USA

Ph: 301-594-2881

Fax: 301-480-8506

sunshinh@nigms.nih.gov

Cha-Mei Tang, PhD\*

President

Creatv MicroTech, Inc.

11609 Lake Potomac Drive

Potomac, MD 20854

USA

Ph: 301-983-1650

Fax: 301-983-6264

cmtinc@erols.com

Zilue Tang, MD PhD

Research Associate

Department of Pharmacology

University of Pittsburgh

200 Lothrop St.

BST E1310

Pittsburgh, PA 15261

USA

Ph: 412-648-2057

Fax: 412-648-1945

ziluetang@hotmail.com

Katherine Tepperman, PhD

Professor

Biological Sciences

University of Cincinnati

Department of Biological Sciences

University of Cincinnati

P.O. Box 210006

Cincinnati, OH 45221-0006

USA

Ph: (513)556-9742

Fax:

katherine.tepperman@uc.edu

Elizabeth C. Theil, PhD

Senior Research Scientist

Children\'s Hospital of Oakland Research Institute

5700 Martin Luther King, Jr Way

Oakland, CA 94609-1673

USA

Ph: (510) 450-7670

Fax: (510) 597-7131

etheil@chori.org

Katherine H. Thompson, PhD

Senior Research Associate

Chemistry Department

The Medicinal Inorganic Chemistry Group

2036 Main Mall

Vancouver, BC V6T 1Z1

CAN

Ph: 604-822-1776

Fax: 604-822-2847

kthompso@chem.ubc.ca

Khristy Thompson, PhD

Postdoctoral Fellow

Department of Neuroscience & Anatomy, H109

Pennsylvania State University College of Medicine

500 University Drive

Hershey, PA 17033

USA

Ph: (717) 531-5203

Fax: (717) 531-5184

kjm13@psu.edu

Belgaum S Thyagaraja, PhD\*

Director

Molecular Biology Division

Gene Probe Technologies, Inc.

8551 Ziggy Lane

Gaithersburg - 20877, MD 20877

USA

Ph: 301-990-8980

Fax: 301-990-6997

geneprobe@aol.com

Suzy Torti, PhD

Asst. Prof. Biochemistry

Department of Biochemistry

Wake Forest University

School of Medicine

Medical Center Blvd

Winston-Salem, NC 27157

USA

Ph: 336 716 9357

Fax:

storti@wfubmc.edu

Dat Tran, PhD\*

Asst. Prof. Biochemistry

Chemistry

Princeton University

Department of Chemistry

Princeton University

Princeton, NJ 8544

USA

Ph: 609-258-4083

Fax: 609-258-3890

dtran@princeton.edu

Ah-lim Tsai, PhD

Associate Professor

Internal Medicine, Hematology Division

University of Texas Houston Medical School

Rm. 5290,

6431 Fannin

Houston, TX 77030

USA

Ph: 713 500-6771

Fax: 713 500-6810

ah-lim.tsai@uth.tmc.edu

Thomas Tullius, PhD

Professor

Department of Chemistry

Boston University

590 Commonwealth Avenue

Boston, MA 2215

USA

Ph: (617) 353-2482

Fax: (617) 353-3535

tullius@bu.edu

http://people.bu.edu/tullius

Hilde E. van Gijssel, PhD\*

Visiting postdoctoral fellow

CDI/LCCTP/DBS

National Cancer Institute

Bldg 37, Rm 2A09, NIH

37 Convent Dr, MSC 4255

Bethesda, MD 20892-4255

USA

Ph: 301 435 4527

Fax: 301 402 8230

vangijsh@mail.nih.gov

Ravi K. Varma, PhD\*

Chemist and Project Officer

Drug Synthesis and Chemistry Branch

National Cancer Institute

Room 5014

6116 Executive Boulivard

Rockville, MD 20852

USA

Ph: 301-435-9159

Fax: 301-480-4817

varmar@dtpepn.nci.nih.gov

http://www.nci.nih.gov OR www.nih.gov

Steven Vazhev

tarana 113/33

kostanai, ko 458000

kazak

Martin Verbeet

Leiden Institute of Chemistry

Leiden University

Metallo-protein and Protein engineering group

Gorlaeus Laboratories

Einsteinweg 55 / P.O. Box 9502

Leiden, The Netherlands, RA 2300 RA

Ph: 31 71 5274434

Fax: 31 71 5274349

http://wwwchem.leidenuniv.nl/metprot/

Anil Verma, PhD

Postdoc fellow

LCMB

NIH

Bldg. 10, Rm \# 10D08

10 center Dr, MSC 1855

Bethesda, MD 20892

USA

Ph: 301-435-2930

Fax:

vermaa@mail.nih.gov

Ronald E Viola, PhD

Professor

Department of Chemistry

University of Akron

190 E. Buchtel Commons

Akron, OH 44325

USA

Ph: 215-898-2227

Fax: 215-573-2112

rviola@uakron.edu

www.chemistry.uakron.edu/viola/group_site

Dharmesh Vishrolia\*

Indian Board of Alternative Medicines

USA

jdbom@hotmail.com

William E. Walden

University of Illinois at Chicago

Department of Microbiology and Immunology

835 South Wolcott

Chicago, IL 60612

USA

Ph: (312) 996-8576

Fax: (312) 996-6415

wwalden@uic.edu

Karla J. Wasserloos\*

University of Pittsburgh School of Medicine

Dept of Pharmacology

200 Lothrop Street

Pittsburgh, PA 15261

USA

\(412\) 648-2057

kaw7+@pitt.edu

Nancy L. Wengenack\*

Graduate student

Biochemistry and Molecular Biology

Mayo Clinic and Foundation

549 Plummer Building

200 S.W. First Street

Rochester, MN 55905

USA

Ph: 507-284-2289

Fax: 507-284-8286

wengenack.nancy@mayo.edu

T. David Westmoreland, PhD

Assoc. Prof.

Chemistry

Wesleyan University

Hall-Atwater Laboratories

Middletown, CT 6459

USA

Ph: 860-685-2743

Fax: 860-685-2211

westmoreland@wesleyan.edu

Angela Wilks, MD

Assistant Professor

Department of Pharmaceutical Sciences

University of Maryland

20 North Pine Street

Baltimore, MD 21201-1180

USA

Ph: 410-706-2537

Fax: 410-706-0346

awilks@rx.umaryland.edu

Gail R. Willsky, PhD

Associate Professor

Biochemistry

SUNYat Buffalo Sch.of Med.and Biomedical Science

Dept. of Biochemistry SUNY at Buffalo

140 Farber Hall

Buffalo, NY 14214

USA

Ph: 716-829-2969

Fax: 716-829-2725

gwillsky@acsu.buffalo.edu

Mary K. Wolpert, PhD

Chief, Grants & Contracts Operations Branch

Division of Cancer Treatment & Diagnosis

National Cancer Institute

Executive Plaza North 841

6130 Executive Boulevard

Bethesda, MD 20892-7456

USA

Ph: 301-496-8783

Fax: 301-402-5200

wolpertm@exchange.nih.gov

Edward H. Wong\*

University of New Hampshire

Durham, NH 03824

USA

Ph: 603-862-1788

ehw@christa.unh.edu

William H. Woodruff, PhD\*

Laboratory Fellow

Bioscience Division

Los Alamos National Lab

Michelson Resource

Mail Stop J586

Los Alamos, NM 97505

USA

Ph: 505-665-2557

Fax: 505-667-0851

<woody@lanl.gov>

Edward Wu, PhD\*

Postdoctoral research

Drug Resistance Program

National Cancer Institute

Room 104

Building 539

NCI-FCRDC

Frederick, MD 21702

USA

Ph: 301-846-1611

Fax: 301-846-5991

wu@cricket.ncifcrf.gov

Annette B. Wysocki, PhD\*

Laboratory Chief

Wound Healing Laboratory

NIH

9 Center Drive MSC 0967

Building 9, Room 1W125

Bethesda, MD 20892-0967

USA

Ph: 301-402-3583

Fax: 301-435-3435

annette_wysocki@nih.gov

Jenny J. Yang, PhD

Assistant Professor

Department of Chemistry

Georgia State University

50 Decatur Street

Atlanta, GA 30303

USA

Ph: 404-651-4620

Fax: 404-651-2751

chejjy@panther.gsu.edu

Hyung-Soon Yim

National Institutes of Health

NHLBI

0000

Bethesda, MD 20892

USA

Ph: 301-496-8862

Fax: 301-496-0599

yimh@gwgate.nhlbi.nih.gov

Moon Yim

NHLBI

USA

Ph: 301-496-9494

Alexander Todorov Yordanov, PhD

CRTA fellow

NCI,ROB,Radioimmune & Inorganic Chemistry Section

National Institutes of Health

Bldg 10 Room B3B69

10 Center Dr.

Bethesda, MD 20892

USA

Ph: (301) 496-6494

Fax: (301) 402-1923

yordanov@box-y.nih.gov

Jeffrey M. Zaleski, PhD

Assistant Professor

Chemistry

Indiana University

800 E. Kirkwood Ave.

Indiana University-Bloomington

Bloomington, IN 47405

USA

Ph: 812-855-2134

Fax: 812-855-7148

zaleski@indiana.edu

Deborah Zamble\*

Harvard Medical School

LHRRB-318

Boston, MA 02115

USA

Ph: 617-432-0931

Fax: 617-432-0556

zamble@walsh.med.harvard.edu

Hong Zhang,

Georgetown University

USA

Ph: 202-687-4864

Lin Zhang,

Z Biomed

USA

Ph: 301-260-0622

Tongqing Zhou, PhD

Research Associate

Biochemistry and Molecular Biology

Wayne State University School of Medicine

540 E. Canfield Avenue

Detroit, MI 48201-1928

USA

Ph: (313)577-0618

Fax: (313)577-2765

tzhou@med.wayne.edu

http://boatman.med.wayne.edu/tongqing

Marc Zimmer, PhD

Prof.

Chemistry Department

Connecticut College

270 Mohegan Ave.

New London, CT 6320

USA

Ph: 860-439-2476

Fax: 860-439-2477

mzim@conncoll.edu

http://conncoll.edu/ccacad/zimmer/MZ-8/MZ-8.html

Steven J. Zullo, PhD\*

SSF

LBG-NIMH-NIH

Bldg 10, Rm 2d56

Bethesda, MD 20892

USA

Ph: 301-435-3576

Fax: 301-480-9862

<zullo@helix.nih.gov>

Todd Zwillich

Science Writer

Science Magazine

1954 Calvert St.

Washington, DC 20009

USA

Ph: 202-232-0827

Fax: 509-463-3405

<toddz@erols.com>

\*Registered, but unable to attend or volunteered to attend by
videocast. Because of a mix-up in badge production, it is not possible
to be certain that all others actually did attend.