bluuebunny/crossref_metadata_2025_split huggingface dataset:
The NMR‐derived conformation of neuropeptide AF, an orphan G‐protein coupled receptor peptide
Authors: Miskolzie Mark , Kotovych George 
Published: May 2003

AbstractThe tertiary structure of the pain modulating and anti‐opiate neuropeptide, human neuropeptide AF (NPAF) (the sequence is AGEGLNSQFWSLAAPQRF–NH2), was determined by 1H‐NMR. The structure of NPAF was determined in two solvent systems, namely 50%/50% trifluoroethanol‐d3/H2O (TFE/H2O) and in the cell membrane mimetic micelle, sodium dodecylsulfate‐d25 (SDS). The receptor for NPAF is an orphan G‐protein coupled receptor, and the micellar SDS solvent system was used to emulate the cell membrane surface in line with the Cell Membrane Compartments Theory proposed by R. Schwyzer (Biopolymers, 1995, Vol. 37, pp. 5–16). In both solvent systems, NPAF was found to be primarily α‐helical within the central portion of the molecule, from Asn6 to Ala14. The N‐terminus was random in both solvent systems. In the SDS solution, the C‐terminal tetrapeptide was structured and formed a type I β‐turn, whereas in TFE/H2O it was unstructured, showing the importance of the C‐terminal tetrapeptide in receptor recognition. NPAF was found to associate with SDS, and was shown to be near the surface of the micelle by spin label studies with 5‐doxyl‐stearic acid. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 201–215, 2003
Molecular dynamics simulation studies of cytochrome b5 from outer mitochondrial and microsomal membrane
Authors: Lee Kyung‐Hoon , Kuczera Krzysztof 
Published: May 2003

AbstractTwo forms of cytochrome b5 have been identified, associated with the outer membrane of liver mitochondria (OM cyt b5) and with the membrane of the endoplasmic reticulum (microsomal, Mc cyt b5). These proteins have very similar structures, but differ significantly in physical properties, with the OM cyt b5 exhibiting a more negative reduction potential, higher stability, and stronger interactions with the heme. We perform molecular dynamics simulations to probe the structures and fluctuations of the two proteins in solution, to help explain the observed physical differences. We find that the structures of the two proteins, highly similar in the crystal, differ in position of a surface loop involving residues 49–51 in solution. Hydrophobic residues Ala‐18, Ile‐32, Leu‐36, and Leu‐47 tend to cluster together on the surface of rat OM cyt b5, blocking water access to the protein interior. In bovine Mc cyt b5, two of these positions, Ser‐18 and Arg‐47, are occupied by hydrophilic residues. This leads to breaking the hydrophobic cluster and allowing the protein to occupy a more open conformation. A measure of this structural transition is the opening of a cleft on the protein surface, which is 5 Å wider in the OM cyt b5 simulation compared to the Mc form. The OM protein also appears to have a more compact hydrophobic core in its β‐sheet region. These effects may be used to explain observed stability differences between the two proteins. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 260–269, 2003
Zinc binding in peptide models of angiotensin‐I converting enzyme active sites studied through 1H‐NMR and chemical shift perturbation mapping
Authors: Galanis Athanassios S. , Spyroulias Georgios A. , Pierattelli Roberta , Tzakos Andreas , Troganis Anastassios , Gerothanassis Ioannis P. , Pairas George , Manessi‐Zoupa Evy , Cordopatis Paul 
Published: May 2003

AbstractWe report the design and synthesis through solid phase 9‐flourenylmethoxycarbonyl (Fmoc) chemistry of the two angiotensin‐I converting enzyme active sites possessing the general sequence HEMGHX23EAIGDX3. Their zinc‐binding properties were monitored in solution through high‐resolution 1H‐NMR. The obtained data were analyzed in terms of chemical shift differences. The results indicate that zinc binds to the HEMGH and the EAIGD characteristic motifs, and suggest possible coordination modes of zinc in the native enzyme. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 244–252, 2003
Synthetic peptide vaccine and antibody therapeutic development: Prevention and treatment of Pseudomonas aeruginosa
Authors: Cachia Paul J. , Hodges Robert S. 
Published: May 2003

AbstractPseudomonas aeruginosa and Pseudomonas maltophilia account for 80% of opportunistic infections by pseudomonads. Pseudomonas aeruginosa is an opportunistic pathogen that causes urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia, and a variety of systemic infections, particularly in patients with severe burns, and in cancer and AIDS patients who are immunosuppressed. Pseudomonas aeruginosa is notable for its resistance to antibiotics, and is therefore a particularly dangerous pathogen. Only a few antibiotics are effective against Pseudomonas, including fluoroquinolones, gentamicin, and imipenem, and even these antibiotics are not effective against all strains. The difficulty treating Pseudomonas infections with antibiotics is most dramatically illustrated in cystic fibrosis patients, virtually all of whom eventually become infected with a strain that is so resistant that it cannot be treated. Since antibiotic therapy has proved so ineffective as a treatment, we embarked on a research program to investigate the development of a synthetic peptide consensus sequence vaccine for this pathogen. In this review article we will describe our work over the last 15 years to develop a synthetic peptide consensus sequence anti‐adhesin vaccine and a related therapeutic monoclonal antibody (cross‐reactive to multiple strains) to be used in the prevention and treatment of P. aeruginosa infections. Further, we describe the identification and isolation of a small peptide structural element found in P. aeruginosa strain K (PAK) bacterial pili, which has been proven to function as a host epithelial cell‐surface receptor binding domain. Heterologous peptides are found in the pili of all strains of P. aeruginosa that have been sequenced to date. Several of these peptide sequences have been used in the development of an consensus sequence anti‐adhesin vaccine targeted at the prevention of host cell attachment and further for the generation of a monoclonal antibody capable of prevention and treatment of existing infections. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 141–168, 2003
Grb2 SH2 domain‐binding peptide analogs as potential anticancer agents
Authors: Lung Feng‐Di T. , Tsai Jya‐Yin 
Published: May 2003

AbstractThe growth factor receptor‐bound protein 2 (Grb2) plays an important role in the Ras signaling pathway. Several proteins were found to be overexpressed by oncogenes in the Ras signaling pathway, rendering Grb2 a potential target for the design of antitumor agents. Blocking the interaction between the phosphotyrosine‐containing activated receptor and the Src‐homology 2 (SH2) domain of Grb2 thus constitutes an important strategy for the development of potential anticancer agents. X‐ray, NMR structural investigations, and molecular modeling studies have provided the target structure of Grb2 SH2 domain—alone or complexed with a phosphotyrosine‐containing peptide—which is useful for the structure‐based design of peptides or peptidomimetics with high affinity for the Grb2 SH2 domain. We review here the variety of approaches to Grb2 SH2 pepide inhibitors developed with the aim of interrupting Grb2 recognition. Inhibitory effects of peptide analogs on the Grb2 SH2 domain and their binding affinities for Grb2 SH2 were determined by ELISA, cell‐based assays, or Surface Plasman Resonance (SPR) technology. Results of theses studies provide important information for further modifications of lead peptides, and should lead to the discovery of potent peptides as anticancer agents. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 132–140, 2003
Oligopeptide inhibition of class I ribonucleotide reductases
Authors: Cooperman Barry S. 
Published: May 2003

AbstractClass I ribonucleotide reductases (RRs), which are well‐recognized targets for cancer chemotherapeutic and antiviral agents, are composed of two different subunits, R1 and R2, and are inhibited by oligopeptides corresponding to the C‐terminus of R2, which compete with R2 for binding to R1. These peptides specifically inhibit the RRs from which they are derived, and closely homologous RRs, but do not inhibit less homologous RRs. Here we review results obtained for oligopeptide inhibition of RRs from several sources, including related x‐ray, NMR, and modeling results. The most extensive studies have been performed on herpes simplex virus‐RR (HSV‐RR) and mammalian‐RR (mRR). A common model fits the data obtained for both enzymes, in which the C‐terminal residue of the oligopeptide (Leu for HSV‐RR, Phe for mRR) binds with high specificity to a narrow and deep hydrophobic subsite, and two or more hydrophobic groups at the N‐terminal portion of the peptide bind to a broad and shallow second hydrophobic subsite. The studies have led to the development of highly potent and specific inhibitors of HSV‐RR and promising inhibitors of mRR, and indicate possible directions for the development of inhibitors of bacterial and fungal RRs. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 117–131, 2003
Successful identification of novel agents to control infectious diseases from screening mixture‐based peptide combinatorial libraries in complex cell‐based bioassays
Authors: Boggiano César , Reixach Natàlia , Pinilla Clemencia , Blondelle Sylvie E. 
Published: May 2003

AbstractMixture‐based peptide synthetic combinatorial libraries (SCLs) represent a valuable source for the development of novel agents to control infectious diseases. Indeed, a number of studies have now proven the ability of identifying active peptides from libraries composed of thousands to millions of peptides in cell‐based biosystems of varying complexity. Furthermore, progressing knowledge on the importance of endogenous peptides in various immune responses lead to a regain in importance for peptides as potential therapeutic agents. This article is aimed at providing recent studies in our laboratory for the development of antimicrobial or antiviral peptides derived from mixture‐based SCLs using cell‐based assays, as well as a short review of the importance of such peptides in the control of infectious diseases. Furthermore, the use of positional scanning (PS) SCL‐based biometrical analyses for the identification of native optimal epitopes specific to HIV‐1 proteins is also presented. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 103–116, 2003
Dmt and opioid peptides: A potent alliance
Authors: Bryant Sharon D. , Jinsmaa Yunden , Salvadori Severo , Okada Yoshio , Lazarus Lawrence H. 
Published: May 2003

AbstractThe introduction of the Dmt (2′,6′‐dimethyl‐L‐tyrosine)–Tic pharmacophore into the design of opioid ligands produced an extraordinary family of potent δ‐opioid receptor antagonists and heralded a new phase in opioid research. First reviewed extensively in 1998, the incorporation of Dmt into a diverse group of opioid molecules stimulated the opioid field leading to the development of unique analogues with remarkable properties. This overview will document the crucial role played by this residue in the proliferation of opioid peptides with high receptor affinity (Ki equal to or less than 1 nM) and potent bioactivity. The discussion will include the metamorphosis between δ‐opioid receptor antagonists to δ‐agonists based solely on subtle structural changes at the C‐terminal region of the Dmt–Tic pharmacophore as well as their behavior in vivo. Dmt may be considered promiscuous due to the acquisition of potent μ‐agonism by dermorphin and endomorphin derivatives as well as by a unique class of opioidmimetics containing two Dmt residues separated by alkyl or pyrazinone linkers. Structural studies on the Dmt–Tic compounds were enhanced tremendously by x‐ray diffraction data for three potent and biologically diverse Dmt–Tic opioidmimetics that led to the development of pharmacophores for both δ‐opioid receptor agonists and antagonists. Molecular modeling studies of other unique Dmt opioid analogues illuminated structural differences between δ‐ and μ‐receptor ligand interactions. The future of these compounds as therapeutic applications for various medical syndromes including the control of cancer‐associated pain is only a matter of time and perseverance. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71:86–102, 2003
Sequence‐dependent solution structure and motions of 13 TATA/TBP (TATA‐box binding protein) complexes
Authors: Strahs Daniel , Barash Danny , Qian Xiaoliang , Schlick Tamar 
Published: May 2003

AbstractThe TATA element is a well‐known example of a DNA promoter sequence recognized by the TATA box binding protein (TBP) through its intrinsic motion and deformability. Although TBP recognizes the TATA element octamer unusually (through the minor groove, which lacks the distinctive features of the major groove), single base‐pair replacements alter transcriptional activity. Recent crystallographic experiments have suggested that TATA/TBP complexes differing by a single base pair retain substantial structural similarity despite their functional differences in activating transcription. To investigate the subtle role of sequence‐dependent motion within the TATA element and certain aspects of its effect on assembly of the transcriptional complex, we examine 5‐ns dynamics trajectories of 13 variant TATA/TBP complexes differing from each other by a single base pair. They include the wild‐type (WT) adenovirus 2 major late promoter (AdMLP) TATA element, TATAAAAG (the octamer specifies positions −31 to −24 with respect to the transcription initiation site), and the variants A31 (i.e., AATAAAAG), T30, A29, C29, G28, T28, T27, G26, T26, C25, T25, and T24. Our simulated TATA/TBP complexes develop sequence‐dependent structure and motion trends that may lead to favorable orientations for high‐activity variants (with respect to binding TFIIA, TFIIB, and other transcription factors), while conversely, accelerate dissociation of low‐activity TATA/TBP complexes. The motions that promote favorable geometries for preinitiation complexes include small rotations between TBP's N‐ and C‐terminal domains, sense strand DNA backbone “slithering,” and rotations in TBP's H2 and H2′ helices. Low‐activity variants tend to translate the H1 and H1′ helices and withdraw the intercalating phenylalanines. These cumulative DNA and protein motions lead to a spatial spread of complex orientations up to 4 Å; this is associated with an overall bend of the variant TATA/TBP complexes that spans 93° to 110° (107° for the crystal reference). Taken together, our analyses imply larger differences when these local structural and bending changes are extended to longer DNA (upstream and downstream) and suggest that specific local TATA/TBP motions (e.g., shifts in TBP helices and TATA bases and backbone) play a role in modulating the formation and maintenance of the transcription initiation complex. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 216–243, 2003
Homology model of the CB1 cannabinoid receptor: Sites critical for nonclassical cannabinoid agonist interaction
Authors: Shim Joong‐Youn , Welsh William J. , Howlett Allyn C. 
Published: May 2003

AbstractAssociation of cannabimimetic compounds such as cannabinoids, aminoalkylindoles (AAIs), and arachidonylethanolamide (anandamide) with the brain cannabinoid (CB1) receptor activates G‐proteins and relays signals to regulate neuronal functions. A CB1 receptor homology model was constructed using the published x‐ray crystal structure of bovine rhodopsin (Palczewski et al., Science,2000, Vol. 289, pp. 739–745) in the conformation most likely to represent the “high‐affinity” state for agonist binding to G‐protein coupled receptors (GPCRs). A molecular docking approach that combined Monte Carlo and molecular dynamics simulations was used to identify the putative binding conformations of nonclassical cannabinoid agonists, including AC‐bicyclic CP47497 and CP55940, and ACD‐tricyclic CP55244. Placement of these ligands was based upon the assumption of a critical hydrogen bond between the A‐ring OH and the side chain N of Lys192 in transmembrane helix 3. We evaluated two alternative binding conformations, C3‐in and C3‐out, denoting the directionality of the ligand C3 side chain within the receptor with respect to the inside or the outside of the cell. Assuming both the C3‐in or C3‐out conformation, the calculated ligand–receptor binding energy (ΔEbind) was correlated with the experimentally observed binding affinity (Ki) for a series of nonclassical cannabinoid agonists. The C3‐in conformation was marginally better than the alternative C3‐out conformation in predicting the rank order of the tested nonclassical cannabinoid analogs. Adopting the C3‐in conformation due to the greater number of receptor interactions with known pharmacophoric elements of the ligand, key residues were identified comprising the presumed hydrophobic pocket that interacts with the C3 side chain of cannabinoid agonists. Key hydrogen bonds would form between both K3.28(192) and E(258) and the A‐ring OH, and between Q(261) and the C‐ring C‐12 hydroxypropyl. In summary, the present study represents one of the first attempts to construct a homology model of the CB1 cannabinoid receptor based upon the published bovine rhodopsin x‐ray crystal structure and to elucidate the putative ligand binding site for nonclassical cannabinoid agonists. We postulated sites of the CB1 receptor critical for the ligand interaction, including the hydrophobic pocket interacting with the key pharmacophoric moiety, the C3 side chain. More work is needed to delineate between two alternative (and possibly other) binding conformations of the nonclassical cannabinoid ligands within the CB1 receptor. The present study provides a consistent framework for further investigation of the CB1 receptor–ligand interaction and for the study of CB1 receptor activation. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 169–189, 2003
An autocatalytic reaction as a model for the kinetics of the aggregation of β‐amyloid
Authors: Sabaté Raimon , Gallardo Montserrat , Estelrich Joan 
Published: May 2003

AbstractAlzheimer's disease is the commonest form of senile dementia, affecting almost 20 million people worldwide. This neurodegenerative disorder is characterized by amyloid deposition in senile plaques, composed primarily of fibrils of an aggregated peptide, β‐amyloid. Fibrillation of β‐amyloid is a nucleation‐dependent polymerization process, which is controlled by two kinetics parameters: the nucleation rate and the elongation or growth rate. As the kinetics of fibrillation is strongly dependent on the presence of trace amounts of fibrils, we suggest that the aggregation of β‐amyloid is a model of autocatalytic reaction. A mathematical analysis, permitting quantitative monitoring of the kinetics of fibrillogenesis of β‐amyloid, nucleation, and elongation constants, is presented. The model was checked by applying it to the aggregation of the fragment 1–40 of the β‐amyloid. Understanding of these rate constants may facilitate the study of the effect of substances used for controlling fibril creation and growth. The disaggregating effect of dodecyl trimethylammonium bromide, a cationic surfactant, was easily quantified by means of the model. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71:190–195, 2003
Mechanism of bactericidal and fungicidal activities of textiles covalently modified with alkylated polyethylenimine
Authors: Lin Jian , Qiu Shuyi , Lewis Kim , Klibanov Alexander M. 
Published: May 2003

AbstractOur previous studies have led to a novel “nonrelease” approach to making materials bactericidal by covalently attaching certain moderately hydrophobic polycations to their surfaces. In the present work, this strategy is extended beyond the heretofore‐used nonporous materials to include common woven textiles (cotton, wool, nylon, and polyester). Pieces of such cloths derivatized with N‐hexylated+methylated high‐molecular‐weight polyethylenimine (PEI) are strongly bactericidal against several airborne Gram‐positive and Gram‐negative bacteria. In contrast, the immobilized and N‐alkylated PEIs of low molecular weight have only a weak, if any, bactericidal activity. These findings support a mechanism of the antibacterial action whereby high‐molecular‐weight and hydrophobic polycationic chains penetrate bacterial cell membranes/walls and fatally damage them. The bactericidal textiles prepared herein are lethal not only to pathogenic bacteria but to fungi as well. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 168–172, 2003.
Identification and comparison of aerobic and denitrifying polyphosphate‐accumulating organisms
Authors: Zeng Raymond J. , Saunders Aaron M. , Yuan Zhiguo , Blackall Linda L. , Keller Jürg 
Published: May 2003

AbstractTwo laboratory‐scale sequencing batch reactors (SBRs) were operated for enhanced biological phosphorus removal (EBPR) in alternating anaerobic–aerobic or alternating anaerobic–anoxic modes, respectively. Polyphosphate‐accumulating organisms (PAOs) were enriched in the anaerobic–aerobic SBR and denitrifying PAOs (DPAOs) were enriched in the anaerobic–aerobic SBR. Fluorescence in situ hybridization (FISH) demonstrated that the well‐known PAO, “Candidatus Accumulibacter phosphatis” was abundant in both SBRs, and post‐FISH chemical staining with 4,6‐diamidino‐2‐phenylindol (DAPI) confirmed that they accumulated polyphosphate. When the anaerobic–anoxic SBR enriched for DPAOs was converted to anaerobic–aerobic operation, aerobic uptake of phosphorus by the resident microbial community occurred immediately. However, when the anaerobic–aerobic SBR enriched for PAOs was exposed to one cycle with anoxic rather than aerobic conditions, a 5‐h lag period elapsed before phosphorus uptake proceeded. This anoxic phosphorus‐uptake lag phase was not observed in the subsequent anaerobic–aerobic cycle. These results demonstrate that the PAOs that dominated the anaerobic–aerobic SBR biomass were the same organisms as the DPAOs enriched under anaerobic–anoxic conditions. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 140–148, 2003.
Protein loading, elution, and resolution behavior in a novel device that integrates ultrafiltration and chromatographic separation
Authors: Dai Xiao‐Ping , Majumdar Sudipto , Luo Robert G. , Sirkar Kamalesh K. 
Published: May 2003

AbstractHollow fiber membranes and chromatographic resin beads are commonly employed in a variety of bioseparation processes. A new class of integrated separation devices is being studied in which the shell side of a hollow fiber device is filled with adsorbents/chromatographic resin beads. Such devices and the corresponding separation methods integrate feed broth clarification by the microfiltration/ultrafiltration membrane with bioproduct purification by the shell‐side resin beads either as an adsorbent or as beads in elution chromatography. A mathematical model has been developed for the prediction of the chromatographic behavior of such an integrated device. Simulations have been done to study the effects of axial dispersion, feed flow rate, water permeation rate, fiber packing density, and void fraction. Numerical solutions were obtained by solving the governing equations. This model can reasonably describe the concentration profiles as well as the breakthrough and elution behaviors in the integrated device. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 125–139, 2003.