bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential response of murine CD4+CD25+ and CD4+CD25– T cells to dexamethasone‐induced cell death
Authors: Chen Xin , Murakami Takaya , Oppenheim Joost J. , Howard O. M. Zack
Published: February 2004

To evaluate the in vivo effect of immunosuppressive glucocorticoids on CD4+CD25+ T regulatory cells, we injected dexamethasone (Dex) into BALB/c mice. Administrationof Dex enhanced the proportion of CD4+CD25+ cells and the ratio of CD4+CD25+ cells to CD4+CD25– cells in the lymphoid organs, especially in thethymus. This correlates with our in vitro observation that CD4+CD25+ T cells express higher levels of glucocorticoid receptor and Bcl‐2, and are therefore more resistant to Dex‐mediated cell death than CD4+CD25– T cells. Furthermore, IL‐2 selectively protected CD4+CD25+ T cells from Dex‐induced cell death, while IL‐7 and IL‐15 didnot exert preferential protective effects. Dex‐treated CD4+CD25+ T cells expressed higher levels of intracellular CTLA‐4 and surface glucocorticoid‐induced TNF receptor than fresh CD4+CD25+ T cells, but still failed to respond to TCR stimulation and inhibited proliferation of CD4+CD25– T cells. These results suggest that, in addition to suppressing cytokine transcription, Dex treatment is permissive for the survival of functional CD4+CD25+ T regulatory cells, and this property may contribute to the anti‐inflammatory and immunosuppressive efficacy of glucocorticoids. Our data also suggest that selective protection of CD4+CD25+ T cell from apoptosis may constitute a role in immune tolerance for IL‐2.
Pinpointing IL‐4‐independent acquisition and IL‐4‐influenced maintenance of Th2 activity by CD4 T cells
Authors: Cunningham Adam F. , Serre Karine , Toellner Kai‐Michael , Khan Mahmood , Alexander James , Brombacher Frank , MacLennan Ian C. M.
Published: February 2004

Naive CD4 T cells develop Th2 activity early in primary responses to alum‐precipitated proteins by producing IL‐4 mRNA and inducing B cells to produce γ1 and ϵ switch transcripts. BothIL‐4‐dependent and IL‐4‐independent pathways for IL‐4 induction are recognized, but their relative contribution to the different phases of primary Th2 responses in vivo is uncertain. We show the primary induction of IL‐4 synthesis in lymph nodes responding to alum‐precipitated protein is overwhelmingly in antigen‐specific CD4 T cells and is unimpaired in IL‐4Rα–/– mice, which can produce but do not respond to IL‐4 and IL‐13. Ig class‐switching in extra‐follicular responses, reflecting Th2 activity, is also unimpaired in these mice. By contrast, 7 days after immunization — when T cells are selecting B cells in germinal centers and T cell priming has occurred — non‐responsiveness to IL‐4 is associated with smaller germinal centers, increased levels of T‐bet andγ2a switch transcripts and reduced γ1 and ϵ transcripts. These data indicate that Th2 characteristics acquired during T cell priming and the initial CD4 T cell interaction with B cells are largely IL‐4‐independent, whereas IL‐4 production induced during priming has a significant role in maintaining the Th2 phenotype as T cells select B cells in germinal centers.
The Toll‐like receptor ligand MALP‐2 stimulates dendritic cell maturation and modulates proteasome composition and activity
Authors: Link Claudia , Gavioli Riccardo , Ebensen Thomas , Canella Alessandro , Reinhard Elena , Guzmán Carlos A.
Published: February 2004

A 2‐kDa synthetic derivative of the macrophage‐activating lipopeptide (MALP‐2) from Mycoplasma fermentans is a potent inducer of monocytes/macrophages and improves the immunogenicity of antigens co‐administered by systemic and mucosal routes. Dendritic cells (DC) are the most potent antigen‐presenting cells, which are able to prime naive T cells in vivo. To elucidate the underlying mechanisms of MALP‐2 adjuvanticity, we analyzed its activity on bone marrow‐derived murine DC. In vitro stimulation of immature murine DC with MALP‐2 resulted in the induction of maturation with up‐regulated expression of MHC class II, costimulatory (CD80, CD86) and adhesion (CD40, CD54) molecules. MALP‐2 also enhances the secretion of cytokines (IL‐1α, IL‐6 and IL‐12), and increases DC stimulatory activity on naive and antigen‐specific T cells. Further studies demonstrated that MALP‐2 treatment of DC results in a dose‐dependent shift from the protein pattern of proteasomes to immunoproteasomes (up‐regulation of LMP2, LMP7 and MECL1), which correlates with an increased proteolytic activity. Thus, the adjuvanticity of MALP‐2 can be mediated, at least in part, by the stimulation of DC maturation, which in turn leads to an improved antigen presentation. Therefore, MALP‐2 is a promising molecule for the development of immune therapeutic or prophylactic interventions.
Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response
Authors: Hensmann Meike , Li Ching , Moss Catherine , Lindo Viv , Greer Fiona , Watts Colin , Ogun Solabomi A. , Holder Anthony A. , Langhorne Jean
Published: February 2004

The 19 kDa C‐terminal fragment of the malaria parasite merozoite surface protein 1 (MSP119) is a leading malaria vaccine candidate. In rodents, high antibody levels to this protein confer protective immunity, and can be generated by immunization with the antigen in adjuvants. In natural human infections, however, MSP119‐specific antibody responses can be short‐lived andcomparatively low, despite repeated exposure to infection. The tightly folded structure of MSP119 is stabilized by five or six disulfide bonds. These bonds impede antigen processing and, thereby, may affect the generation of CD4+ T cells providing help for B cells. Asparagine endopeptidase could digest unfolded, but not native MSP119 in vitro. Immunization with unfolded MSP119 resulted in a faster antibody response, and a combination of unfolded and native MSP119 increased antibody responses to the native form. Immunization with either form of the antigen activated similar numbers of CD4+ T cells, but, unlike the antibody response, CD4+ T cells immunized with one form of MSP119 were able to respond in vitro to the other form of the protein. Although the reduced form of MSP119 does not induce protective antibodies, our data suggest that inclusion of unfolded protein may improve the efficacy of MSP119 as a vaccine.

See correction http://dx.doi.org/10.1002/eji.200490004
Induction of FOXP3‐expressing regulatory CD4pos T cells by human mature autologous dendritic cells
Authors: Verhasselt Valérie , Vosters Olivier , Beuneu Claire , Nicaise Charles , Stordeur Patrick , Goldman Michel
Published: February 2004

Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide‐matured DC and CD4pos T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4pos T cell activation, we observed that a significant fraction of CD4pos T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL‐2, IFN‐γ, IL‐10 and TGF‐β. Furthermore, CD4pos T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third‐party stimulators were spared. The generation of CD4pos T cells with regulatory function by autologous stimulation did not require the presence of natural CD4posCD25pos regulatory T cells. In addition, the acquisition ofregulatory function by CD4posCD25neg T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.
Viral infection and Toll‐like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte‐derived dendritic cells
Authors: Coccia Eliana M. , Severa Martina , Giacomini Elena , Monneron Danièle , Remoli Maria Elena , Julkunen Ilkka , Cella Marina , Lande Roberto , Uzé Gilles
Published: February 2004

In humans, the type I interferon (IFN) family consists of 13 IFN‐α subtypes, IFN‐β and IFN‐o the newly discovered IFN‐like family consists of IFN‐λ1, ‐λ2 and ‐λ3. We have investigated the expression of type I and λ IFN genes following virus infections or Toll‐like receptor (TLR) triggering in monocyte‐derived DC (MDDC) and plasmacytoid DC (pDC). We found thatall IFN‐α, ‐β, ‐o and ‐λ subtypes are expressed in influenza‐virus‐infected MDDC or pDC. Conversely, differential type I IFN gene transcription was induced in MDDC and pDC stimulated by specific TLR agonists. TLR‐9 stimulation by CpG DNA induced the expression of all IFN‐α, ‐β, ‐o and ‐λ subtypes in pDC, whereas TLR‐4 stimulation by LPS, or TLR‐3 stimulation bypoly I:C, induced only IFN‐β and IFN‐λ gene expression in MDDC. The expression pattern of IFN regulatory factor (IRF)‐5 and IRF‐7 in MDDC and pDC was also determined. IRF‐5 was constitutively expressed in the two DC subsets whereas IRF‐7 was constitutive in pDC but its expression was induced along MDDC maturation. Overall, our data indicate that the coordinated expression of IFN‐λ with IFN‐β would be of crucial importance for the maturation of DC.
Mycobacterium vaccae induces a population of pulmonary CD11c+ cells with regulatory potential in allergic mice
Authors: Adams Victoria C. , Hunt Jon R. F. , Martinelli Roberta , Palmer Rebecca , Rook Graham A. W. , Brunet Laura Rosa
Published: February 2004

The hygiene hypothesis proposes that common, harmless microorganisms, present throughout our evolutionary history, have helped to develop immunoregulatory mechanisms that prevent inappropriateimmune responses by the host. Using a mouse model of allergic pulmonary inflammation, we report that treatment with an ubiquitous saprophytic mycobacterium, Mycobacterium vaccae, significantly reduces allergic inflammation by decreasing type 2 responses such as eosinophilia and IL‐4 expression. Rather than observing an increase in type‐1 cytokine expression, we found elevated production of IL‐10 in the lungs suggesting a role for regulatory T cells. Since induction of these cells may be dependent on APC, we investigated the effects of M. vaccae treatment on pulmonary CD11c+ cells. Increased levels of IL‐10, TGF‐β and IFN‐α mRNA were detected in CD11c+ cells from M. vaccae‐treated allergic mice. We propose that M. vaccae‐induced CD11c+ cells have a potential regulatory role at the site of inflammation through their secretion of immunomodulatory cytokines.
Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice
Authors: Lobito Adrian A. , Lopes Marcela F. , Lenardo Michael J.
Published: February 2004

Mice expressing transgenic T cell receptors (TCR) are used to explore important questions in immunity. However, transgene expression may have unexpected effects. We previously reported a B cell immunodeficiency, comprising decreased B cell numbers and diminished antibody responses, in mice that express a transgenic TCR specific for nicotinic acetylcholine receptor; the mice were generated using cassette vectors designed specifically for transgenic TCR expression [see Kouskoff et al. J. Immunol. Methods 1995. 180: 273–280]. We now show data suggesting that this defect is due to the expression and accumulation of TCR α and β chains inside B cells and induction of an endoplasmic reticulum stress response, causing apoptosis at the pre B‐I and later B cell stage. Thus, inappropriate transgene expression can profoundly affect B cells, leading to a previously undescribed mechanism of immunodeficiency.
Retinoids induce Fas(CD95) ligand cell surface expression via RARγ and nur77 in T cells
Authors: Tóth Beáta , Ludányi Katalin , Kiss Ildikó , Reichert Uwe , Michel Serge , Fésüs László , Szondy Zsuzsa
Published: February 2004

Cells from the CD4+ murine T hybridoma line IP‐12‐7 enter the apoptotic suicide program via the Fas ligand (FasL)/Fas‐mediated pathway upon TCR stimulation. This stimulus regulates the sensitization of the Fas death pathway and the cell surface appearance of preformed FasL. The apoptosis is dependent on new mRNA and protein synthesis and involves up‐regulation of nur77.Two groups of nuclear receptors for retinoic acids (RA) have been identified: retinoic acid receptors (RAR) and retinoid X receptors. IP‐12‐7 cells express RARα and RARγ. Here we show that,in the IP‐12‐7 T cells, RA also induced the expression and DNA binding of nur77, and the cell surface appearance of FasL. The induction was mediated via RARγ. Despite the induced expression of cell surface FasL, only two structurally related RARγ‐selective compounds, CD437 and CD2325, initiated apoptosis in these cells. The lack of apoptosis induction by natural RA was related to the inability of RARγ to sensitize the Fas death‐pathway. Cell surface FasL, however, was able to induce cell death in Fas‐bearing target cells. Natural RA also induced the expression of FasL in phytohemagglutinin‐activated peripheral murine T cells. It is proposed that therapeutically administered RA might induce apoptosis in Fas‐sensitive cells via induction of FasL expression in activated Tcells.
Ex vivo detection of myelin basic protein‐reactive T cells in multiple sclerosis and controls using specific TCR oligonucleotide probes
Authors: Hong Jian , Zang Ying C. Q. , Li Sufang , Rivera Victor M. , Zhang Jingwu Z.
Published: February 2004

T cell reactivity to candidate myelin autoantigens, such as myelin basic protein (MBP), may play an important role in the pathogenesis of multiple sclerosis (MS). Although MBP‐reactive T cellshave been found to undergo in vivo activation in patients with MS, their true precursor frequency in MS is unknown as current frequency analysis is commonly based on the T cell functional responses to MBP. In this study, we developed a TCR sequence‐based ex vivo detection system using colony hybridization with oligonucleotide probes specific for CDR3 of selected T cell clones for the analysis of true T cell precursor frequency in PBMC. The results revealed that the precursor frequency of five independent T cell clones recognizing the immunodominant MBP83–99 region was found to be in the range of 1.6×10–4 in total T cells in three HLA‐DR2 patients with MS compared to that of 0.25×10–4 in HLA‐DR2 healthy individuals. The observed frequency of MBP83–99–reactive T cells in MS patients was considerably higher than those measured in parallel by cell culture‐based analysis (2.3×10–6) or by enzyme‐linked immunospot assay (3.9×10–5) in the same peripheral blood mononuclear cell specimens. Furthermore, the study showed that MBP83–99–reactive T cells detected ex vivo belonged to CD45RA+, CD25+ and CD95– T cell subsets as evidenced by preferential expression of specific TCR transcripts in these cell fractions.
Disulfide bonds in merozoite surface protein 1 of the malaria parasite impede efficient antigen processing and affect the in vivo antibody response
Authors: Hensmann M. , Li C. , Moss C. , Lindo V. , Greer F. , Watts C. , Ogun S. A. , Holder A. A. , Langhorne J.
Published: February 2004

Vol. 34(3) 2004, DOI 10.1002/eji.200324514

Due to a technical error, the wrong affiliations were given for C. Moss and V. Lindo. These are correct as given above.

See original article http://dx.doi.org/10.1002/eji.200324514
The Synthesis of Arylalkyne‐Substituted Tetrapyrazinoporphyrazines and an Evaluation of Their Potential as Photosensitisers for Photodynamic Therapy
Authors: Mitzel Frieder , FitzGerald Simon , Beeby Andrew , Faust Rüdiger
Published: February 2004

New aryl‐terminated octaalkynyl tetrapyrazinoporphyrazines were prepared in three steps starting from functionalised bisarylalkynyl 1,2‐diones. While the tert‐butylphenyl substituents were shown to aid solubility in organic solvents and to reduce chromophore aggregation efficiently, more hydrophilic tetrapyrazinoporphyrazines were obtained through the use of polyethylene glycol‐substituted (PEG‐substituted) phenyl groups. The absorption profiles and the singlet oxygen quantum yields of the acetylenic tetrapyrazinoporphyrazines were determined with a view to assess their suitability for PDT applications. In all cases the presence of the terminal aryl moieties resulted in noticeable bathochromic and hyperchromic shifts of the lowest‐energy absorption maxima to 680 nm and of the extinction coefficients to beyond 320000. If magnesium is coordinated in the centre of the acetylenic tetrapyrazinoporphyrazines the compounds have singlet oxygen quantum yields of 0.40 in THF. With zinc as the central metal ion, the singlet oxygen quantum yields in the same solvent increase to 0.70. The absorption characteristics of the newly prepared chromophores, as well as their ability to generate singlet oxygen, suggest that these phthalocyanine analogues are interesting candidates as PDT‐sensitisers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cycloaddition Reactions of 1,4‐Dihydronaphthalene‐1,4‐epoxide with Cyclohexadiene and 7‐(Methoxycarbonyl)cycloheptatriene: Selectivity in Additions
Authors: Menzek Abdullah , Altundaş Aliye , Çoruh Ufuk , Akbulut Nihat , López Ezequiel M. Vázquez , Hökelek Tuncer , Erdönmez Ahmet
Published: February 2004

Cycloaddition reactions of naphthalene‐1,4‐epoxide (1) with both 7‐(methoxycarbonyl)cycloheptatriene (2) and cyclohexadiene (4) give adducts of type 3 and 5 exclusively. Selectivity was observed for the cycloaddition and bromination reactions, but neighboring group participation also occurrs in the latter. The formation of the products is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Drastic Increase in the Flexibility of Open Host Frameworks of a Steroidal Host Compound upon Shortening Its Spacer
Authors: Kato Kazuaki , Sugahara Michihiro , Tohnai Norimitsu , Sada Kazuki , Miyata Mikiji
Published: February 2004

Nordeoxycholic acid (NDCA), which has a shorter side chain than the steroidal host compound, deoxycholic acid (DCA), forms inclusion crystals with various organic substances at 1:1 or 2:1 host−guest ratios. X‐ray crystallographic studies reveal that four types of host frameworks (bilayer, monolayer, tape, and hexagonal) are generated by NDCA, in stark contrast to the robust and dominant bilayer frameworks formed from DCA, although they have the same functional groups capable of hydrogen bonding. The first three host frameworks are further divided into three, two, and four sub‐types by arrangements of the hydrogen‐bonded host columns, tapes, or layers, respectively. A total of nine types of open host frameworks are observed depending on the nature of the guest compounds. The sizes of the guest compounds induce isomerization of these host frameworks having molecular cavities, which is rationalized by the range of values of PCcavity, which are ratios of the volumes between the guest compound and the host cavities. Such a drastic increase of flexibility of the open host framework by the slight chemical modification from DCA to NDCA deserves attention with respect to crystal engineering. Unique 21 helical assemblies of DCA are linked by the carboxyl group at the side chain to form a robust sheet‐like structural motif. In NDCA, on the other hand, the linkage between the helices becomes impossible because of the shortening of the side chain’s length, which results in destruction of the sheet‐like motif to yield renewed molecular voids among the unique 21 helical assemblies. These remarkable differences in the flexibility of the open host frameworks provide us with a possible strategy for designing of new host compounds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Lycoperdinoside A and B, New Glycosides from the Slime Mold Enteridium lycoperdon
Authors: Řezanka Tomáš , Dvořáková Radmila , Hanuš Lumír O. , Dembitsky Valery M.
Published: February 2004

Two, novel, six‐membered lactone glycosides (lycoperdinoside A and B) were isolated from the slime mold Enteridium lycoperdon. Their structures, including the absolute configurations of the hydroxy and methyl groups, were determined by means of extensive spectroscopic data such as MS, IR, UV, and 1D and 2D NMR spectra and chemical degradation. The compounds have structures containing a β‐L‐amicetosyl‐(1⇄4)‐α‐L‐amicetosyl unit and a β‐L‐amicetosyl‐(1⇄4)‐α‐L‐amicetosyl‐(1⇄4)‐β‐L‐rhodinosyl unit, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of the Trisaccharide and Tetrasaccharide Moieties of the Potent Immunoadjuvant QS‐21
Authors: Zhu Xiangming , Yu Biao , Hui Yongzheng , Schmidt Richard R.
Published: February 2004

The title trisaccharide and tetrasaccharide moieties have been synthesized as part of our research programme to construct the complex triterpenoid saponin QS‐21, a potent immunoadjuvant, which has been used in a series of clinical immunization trials. In view of the unwillingness of glucuronic acid as glycosyl acceptor, the branched glucuronic acid‐containing trisaccharide20was synthesized fromD‐glucose, which was in turn glycosylated at positions 2 and 3, followed by oxidation at position 6, in a linear sequence of 15 steps and in good overall yield. The apiose‐containing tetrasaccharide36was constructed by a linear glycosylation strategy from the non‐reducing terminal sugar,D‐apiose, which was prepared fromD‐xylose by a known procedure, also in a linear sequence of 15 steps. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
SASAPOS Cascades of Perfluorinated Aromatic Carboxylic Acids: Low‐Temperature Decarboxylation Triggered by Electrostatic Effects of Polycationic Ligand Sets
Authors: Pühlhofer Frank G. , Weiss Robert
Published: February 2004

Polycationically substituted derivatives of benzoic and phthalic acids were synthesized for the first time via SASAPOS cascades of the corresponding perfluoro(di)carboxylic acids or acyl chlorides (SASAPOS: self‐activated silyl‐assisted poly‐onio substitution). The carboxylic acids decarboxylate with extreme ease (e.g. at room temperature or below) via the corresponding carboxylates. Electrostatically highly stabilized phenylanion derivatives figure as potent electrofuges in these reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Solvent‐Free Microwave‐Assisted Preparation of Chiral Ionic Liquids from (−)‐N‐Methylephedrine
Authors: Thanh Giang Vo , Pegot Bruce , Loupy André
Published: February 2004

An efficient method for the preparation of chiral ionic liquids based on (1R,2S)‐(−)‐ephedrinium salts under solvent‐free conditions and microwave activation is described. The influence of non‐specifically thermal microwave effects − consistent with mechanistic considerations − is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Regioflexibility in the Functionalization of Multiply Halogenated Quinolines
Authors: Marull Marc , Schlosser Manfred
Published: February 2004

4‐Bromo‐6‐fluoro‐2‐(trifluoromethyl)quinoline (1) and 4‐bromo‐7‐fluoro‐2‐(trifluoromethyl)quinoline (13) were selected as model substrates to explore under what conditions regiochemically exhaustive functionalization reactions can be carried out. This goal was achieved by using trimethylsilyl entities and iodine atoms as the sole auxiliary substituents. The organolithium intermediates could be generated and the protective groups removed without impairing the bromine atom present at the 4‐position. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of 2‐(Arylamino)‐2‐(arylimino)acetamides
Authors: Langer Peter , Schroeder Rita
Published: February 2004

The reaction of 2‐(arylamino)‐2‐oxoacetates with PCl5 afforded 2‐(arylamino)‐2,2‐dichloroacetates. The reaction of these compounds with aniline derivatives allowed a convenient synthesis of a great variety of 2‐(arylamino)‐2‐(arylimino)acetamides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Selective Host Amplification from a Dynamic Combinatorial Library of Oligoimines for the Syntheses of Different Optically Active Polyazamacrocycles
Authors: González‐Álvarez Almudena , Alfonso Ignacio , López‐Ortiz Fernando , Aguirre Ángel , García‐Granda Santiago , Gotor Vicente
Published: February 2004

Two different macrocyclic hosts are amplified and expressed by metal guests from the same dynamic combinatorial library (DCL) of oligoimines. We studied the thermodynamic template effect and the structure of the final compounds by a combination of ESI‐MS, UV and NMR spectroscopy, and X‐ray crystallography techniques. The use of BaIIor CdIImetal salts allows the selective synthesis of dimeric [2+2] or trimeric [3+3] cyclic structures, respectively. We observed a cooperative molding effect for the Cd ion‐templated process. A study of the DCL behavior in situ demonstrated a second level of molecular diversity, based on the imine/α‐methoxyamine equilibrium. This process is probably promoted by metal ion coordination and shows an interesting diastereoselectivity in the formation of the new chiral centers. Semiempirical (PM3) theoretical calculations also support these experimental observations. Reduction of the imine bonds allows the selective preparation and isolation of each macrocyclic polyamine on a synthetic scale and in a one‐pot procedure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
The Superbase‐Mediated Pairwise Substitution of the 2,2′‐ and 6,6′‐Positions in a Biphenyl Derivative
Authors: Schlosser Manfred , Mangano Guiseppe , Leroux Frédéric
Published: February 2004

The superbasic mixture of butyllithium and potassium tert‐butoxide is powerful enough to enable the double proton abstraction from one ortho and one ortho′ position of 4,4′‐di‐tert‐butylbiphenyl. In this way, a series of functionalized derivatives becomes readily accessible, among them 4,4′‐di‐tert‐butylbiphenyldiyl‐2,2′‐dicarboxylic acid (2a) and 4,4′‐di‐tert‐butylbiphenyl‐2,2′‐diol (2d). The latter compound can be subjected again to a superbase‐promoted double metalation, thus giving rise to 2,2′,6,6′‐tetrasubstituted biphenyl derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Acylation of Alkyl Halides and Amino Aldehydes with a Phosphane Oxide‐Based d1‐Synthon
Authors: Brünjes Marco , Kujat Christof , Monenschein Holger , Kirschning Andreas
Published: February 2004

Alkyl iodides and α‐amino aldehydes can be homologated to the corresponding methyl esters and β‐amino methyl esters, including β‐amino‐α‐hydroxy methyl esters, using lithiated (dimethoxymethyl)diphenylphosphane oxide. The primary α,α‐(dimethoxy)diphenylphosphane oxides obtained by this Horner−Wittig type process collapse to give the target esters under proton‐catalyzed conditions in the presence of water. Detailed and carefully conducted mechanistic studies revealed that the diphenylphosphane oxide group is activated by protonation, and acts as the initial leaving group in this process. In the cases of adducts derived from the reaction of the phosphane oxide‐stabilized anion with α‐amino aldehydes, homologation to the β‐amino‐ and β‐amino‐α‐hydroxy methyl esters can be achieved by KOtBu‐mediated elimination to the intermediate O,O‐ketene acetals. These may either be allowed to react with water under acidic conditions to yield the β‐amino methyl esters, or may be treated under the Sharpless asymmetric dihydroxylation conditions to directly furnish the β‐amino‐α‐hydroxy methyl esters. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of (4R,9Z)‐9‐Octadecen‐4‐olide, the Female Sex Pheromone ofJanus integer, and Its Enantiomer
Authors: Shibata Chié , Mori Kenji
Published: February 2004

Enantiomer separation of (±)‐8‐tert‐butyldiphenylsilyloxy‐1‐octyn‐3‐ol was achieved by lipase‐mediated asymmetric acetylation. The resolved (R)‐alkynol was converted into (4R,9Z)‐9‐octadecen‐4‐olide, which was identical with the female sex pheromone of the currant stem girdler (Janus integer). The absolute configuration of the natural pheromone was thus established asR. (4S,9Z)‐9‐Octadecen‐4‐olide was also synthesized, and found to be pheromonally inhibitory. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
A New Entry to Bis‐Tröger’s Bases
Authors: Mas Thierry , Pardo Carmen , Salort Francisca , Elguero José , Torres M. Rosario
Published: February 2004

This paper reports the use of p‐phenylenediamine to prepare bis‐Tröger’s bases. The methyl,nitro‐substituted bis‐Tröger’s base 5, already previously prepared by another procedure, was obtained in fewer steps, although with no improvement in the yield of the desired syn isomer. The symmetric dinitro‐substituted bis‐Tröger’s base 17, which cannot be prepared by the older method, was then synthesized. Its structure was determined by mass spectrometry, 2D NMR spectroscopy, and, in the case of the syn isomer, by X‐ray crystallography. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Red‐ and Blue‐Shifts in Oligo(1,4‐phenyleneethynylene)s Having Terminal Donor−Acceptor Substitutions
Authors: Meier Herbert , Mühling Bastian , Kolshorn Heinz
Published: February 2004

Four series of oligo(1,4‐phenyleneethynylene)s (OPEs), 1−4 (a−d), each having a terminal dialkylamino group as their electron donor, were prepared by applying Sonogashira−Hagihara reactions and a protecting group strategy. To study the influence that the push−pull effect has on the long‐wavelength absorption, three of the four series of OPEs contain terminal acceptor groups (CN, CHO, NO2). Extending the conjugation (increasing the number of repeat units, n) lowers the energy E(n) of the electron transition in the purely donor‐substituted series 1a−4a (bathochromic shift). This effect is superimposed in the push−pull series 1−4 (b−d) by the effect of the intramolecular charge transfer (ICT), which decreases with increasing the distance between the donor and acceptor groups. In the case of the relatively weak acceptor CN, both effects annihilate one another, whereas the reduction of the ICT predominates in the CHO and NO2 series. Therefore, E(n) is virtually independent of n in the CN series 1b−4b and shows a hypsochromic effect in the CHO and NO2 series (1c−4c and 1d−4d, respectively). We rationalize these results based on AM1−INDO/S calculations. The results of the commonly used intuitive VB model having electroneutral and zwitterionic resonance structures are compared with those of a more appropriate MO model having dipole segments at both chain ends. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Highly Regio‐ and Diastereoselective Chromium(0)‐Catalysed Cyclopropanation of 1‐Alkoxy‐1,3‐dienes with Diazo Compounds
Authors: Hahn Norbert D. , Nieger Martin , Dötz Karl Heinz
Published: February 2004

Pentacarbonyl(η2‐cis‐cyclooctene)chromium(0) (1) is an efficient catalyst for diazo decomposition and selective [2+1]‐cycloaddition reactions of the resulting carbene intermediates with electron‐rich dienes. The cyclopropanation of 1‐alkoxy‐1,3‐butadienes 4−8 with 9‐diazo‐9H‐fluorene (2) yields vinylspirocyclopropanes 9−13 in good to excellent yields, as single regioisomers arising from carbene transfer to the less substituted C=C bond. The pentacarbonylchromium‐catalysed cyclopropanation with ethyl α‐diazophenylacetate (3) gives the corresponding vinylcyclopropanecarboxylates 16−20 in very good yields and with exceptionally high trans stereoselectivities (> 95%). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Total Syntheses and Biological Assessment of Macrocyclic Glycolipids
Authors: Fürstner Alois
Published: February 2004

Novel strategies for the synthesis of structurally complex macrocyclic glycolipids are outlined which have opened concise and highly flexible entries into various resin glycosides and sugar‐based macrodiolides. The key design elements consist of either a ring‐closing alkene (RCM) or alkyne metathesis (RCAM) event or a newly developed template‐directed dilactonization reaction. The performance and excellent application profile of these transformations are illustrated by the total syntheses of tricolorin A and G, woodrosin I, sophorolipid lactone, cycloviracin B1, glucolipsin A, and various analogues thereof. A brief survey of the biological activities exerted by these amphiphilic natural products is provided. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Fluorinated Heterocyclic Compounds − The First Example of an Irreversible Ring‐Degenerate Rearrangement on Five‐Membered Heterocycles by Attack of an External Bidentate Nucleophile
Authors: Buscemi Silvestre , Pace Andrea , Pibiri Ivana , Vivona Nicolò , Lanza Camilla Zaira , Spinelli Domenico
Published: February 2004

The reactions of 5‐perfluoroalkyl‐1,2,4‐oxadiazoles 3 with hydroxylamine in DMF give the regioisomeric 3‐perfluoroalkyl‐1,2,4‐oxadiazoles 4 in excellent yields. This process is the first example of ring‐degenerate rearrangement (RDR) occurring on five‐membered heterocycles by attack of an external bidentate nucleophile, which replaces two heteroatoms of the ring. We suggest that an ANRORC‐like mechanism occurs in which the addition of the nucleophilic nitrogen atom (NH2OH) on the C(5) atom of 3 is followed by ring opening and irreversible ring‐degenerate closure by attack of the nucleophilic oxygen atom (=NOH) on the C(3) atom of the original ring, realizing an elegant and efficient synthesis of 4 by a C(3)−C(5) annular switch. Ab initio computations on the starting materials and final products, as well as on the proposed intermediates, support the mechanism and shed light on the features of the reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Asymmetric Synthesis of β‐Amino Acid and Amide Derivatives by Catalytic Conjugate Addition of Aromatic Amines to N‐Alkenoylcarbamates
Authors: Li Kelin , Cheng Xiaohui , Hii King Kuok (Mimi)
Published: February 2004

We report a highly active palladium catalyst for the enantioselective conjugate addition of primary aromatic amines to N‐alkenoylcarbamates, furnishing β‐amino N‐Boc‐amides in extremely high yields (>99 %) and unprecedented optical purity (>99 % ee) with just 2 mol % catalyst loading. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cover Picture: Total Syntheses and Biological Assessment of Macrocyclic Glycolipids (Eur. J. Org. Chem. 5/2004)
Authors: Fürstner Alois
Published: February 2004

The cover picture shows the dried calyx of Ipomoea tuberosa L. (Merremia tuberosa) which gives this plant its descriptive common name “woodrose”. One of its bioactive metabolites is the resin glycoside “woodrosin I” shown in the inset, the first total synthesis of which is summarized as part of the Microreview by A. Fürstner on the chemistry and biology of complex glycolipids on p. 943 ff.
Development of an Amperometric Biosensor for β‐N‐Oxalyl‐L‐α,β‐Diaminopropionic Acid (β‐ODAP)
Authors: Beyene Negussie W. , Moderegger Helmut , Kalcher Kurt
Published: February 2004

An amperometric method for the determination of the neurotoxic amino acid β‐N‐oxalyl‐L‐α,β‐diaminopropionic acid (β‐ODAP) using a screen printed carbon electrode (SPCE) is reported. The electrode material was bulk‐modified with manganese dioxide and used as a detector in flow injection analysis (FIA). The enzyme glutamate oxidase (GlOx) was immobilized in a Nafion‐film on the electrode surface. The performance of the biosensor was optimized using glutamate as an analyte. Optimum parameters were found as: operational potential 440 mV (vs. Ag/AgCl), flow rate 0.2 mL min−1, and carrier composition 0.1 mol L−1 phosphate buffer (pH 7.75). The same conditions were used for the determination of β‐ODAP. The signal was linear within the concentration range 53–855 μmol L−1 glutamate and 195–1950 μmol L−1 β‐ODAP. Detection limits (as 3σ value) for both analytes were 9.12 and 111.0 μmol L−1, respectively, with corresponding relative standard deviations of 3.3 and 4.5%. The biosensor retained more than 73% of its activity after 40 days of on‐line use.
An Investigation into Outer‐Surface Biofouling and Electrode Passivation Effects on Gold Electrodes Modified with Calix[4]resorcinarenetetrathiol and a PEG Derivative on Exposure to Whole Human Blood
Authors: Collyer Stuart , Davis Frank , Lucke Andrew , Stirling Charles J. M. , Higson Séamus P. J.
Published: February 2004

An investigation into the hemo‐biocompatibility of calix[4]resorcinarenetetrathiol and calix‐PEG derivative coatings on gold electrodes is reported, with respect to the detection of the ascorbate ion in aqueous solution. The electrochemical behavior of the ascorbate ion at calix‐modified electrodes is also discussed. Findings show that a facilitated adsorption of ascorbate from solution is seen at calix‐modified gold electrodes. Following exposure to whole human blood, calix‐PEG derivative coatings were seen to offer some protection against both outer‐surface biofouling and electrode passivation effects in comparison to calix[4]resorcinarenetetrathiol counterparts. The individual effects of outer surface biofouling and electrode passivation on exposure to whole blood have been investigated. Our findings suggest that PEG moieties help prevent sorption of the biofouling film, thus possibly minimizing the release of a number of low molecular weight solutes which are thought to be involved with the passivation of electrode responses within clinical bio‐ and chemical sensors.
New Macrocyclic Diamides as Neutral Ionophores for Highly Selective and Sensitive PVC‐Membrane Electrodes for Be2+ Ion
Authors: Shamsipur Mojtaba , Soleymanpour Ahmad , Akhond Morteza , Sharghi Hashem
Published: February 2004

Five recently synthesized macrocyclic diamides were investigated to characterize their ability as beryllium ion carriers in potentiometric PVC‐membrane electrodes. The electrodes based on 1,15‐diaza‐3,4;12,13‐dibenzo‐5,8,11‐trioxabicyclo[13,2,2] heptadecane‐2,14‐dione exhibited a Nernstian response for Be2+ ion over wide concentration ranges (from 3.0×10−6 to 3.0×10−2 M for polymeric membrane electrode, PME, and from 5.0×10−7 to 2.0×10−2 M for coated glassy carbon electrode, CGCE) and very low detection limits (2.0 ×10−6 M for PME and 4.0×10−7 M for (CGCE). The electrodes possess low resistances, fast responses, satisfactory reproducibilities and, most importantly, good selectivities relative to a variety of other common cations. The potentiometric response of the electrodes is independent of pH of test solution in the pH range of 4.0–7.5. The proposed sensors were used to determine beryllium ion in water samples.
Novel Dicyanoargentate Polymeric Membrane Sensors for Selective Determination of Cyanide Ions
Authors: Hassan Saad S. M. , Marzouk S. A. M. , Mohamed Ayman H. K. , Badawy N. M.
Published: February 2004

The construction and general performance characteristics of three novel potentiometric PVC membrane sensors responsive to dicyanoargentate anion are described. The sensors are based on the use of magnesium(II)‐ and iron(II)‐phthalocyanines as neutral ionophores and iron(II)‐bathophenanthroline dicyanoargentate ion‐pair complex as an ion exchanger in plasticized PVC matrices. These sensors exhibit fast, stable and near‐Nernstian response (54–59 mV/decade) for the singly charged dicyanoargentate anion over the concentration range 1×10−2–5.8×10−6 M. Potentiometric responses of sensors based on metal phthalocyanines and iron(II)‐bathophenanthroline are stable over the pH ranges 5–7 and 5–12, respectively. The selectivity of the sensors are fairly good over most common anions. Use of the sensors for potentiometric determination of microgram quantities of cyanide ion after conversion into dicyanoargentate anions shows an average recovery of 99.5% and a mean standard deviation of ±0.5%. Determination of cyanide ions in some exhausted electroplating bath samples gives results that compare favourably well with data obtained using the solid‐state cyanide electrode.
Validation of Some Procedures for Quantifying Platinum at sub‐μg/L Level in Some Real Matrices by Catalytic Adsorptive Stripping Voltammetry
Authors: Desimoni Elio , Brunetti Barbara , Cattaneo Raffaella
Published: February 2004

The potential toxicological properties of platinum group elements, usually present in real matrices at sub‐ng/g level, explain the increasing interest in developing specific and sensitive analytical methods. In this work, a validation study was performed in order to ensure the fitness‐for‐purposes of procedures developed for quantifying platinum in tap water, beer and lettuce using an extremely sensitive method based on catalytic adsorptive stripping voltammetry. The work involved the estimation of selectivity, detection and quantitation limits, range, accuracy (trueness plus precision), uncertainty of measurement (UOM), robustness and recovery. The results are discussed in the light of the most recent literature findings.
Multiresidue Analysis of Pesticides in Environmental Waters by Capillary Electrophoresis Using Simultaneous UV and Electrochemical Detection
Authors: Chicharro M. , Zapardiel A. , Bermejo E. , Sánchez A. , González R.
Published: February 2004

A rapid multiresidue method has been developed for the analysis of eight pesticides (triazines, triazinones and ureas) in environmental waters. A simple end‐column electrochemical detector was used in combination with an available commercial capillary electrophoresis instrument with UV detection. The determination of these pesticides using micellar electrokinetic capillary chromatography (MEKC) with dual electrochemical and UV detection is the first time reported. In both detection systems, a linear range was obtained for the eight pesticides, concentrations lower than 5.0×10−5 mol L−1, in 0.020 mol L−1 boric acid at pH 8.3 and containing 0.025 mol L−1 of sodium dodecylsulfate, to obtain selectivity in the additional separation by micellar distribution process. Under these conditions a lower detection limit than 2.0×10−6 mol L−1 (0.15 pmol of pesticide) was achieved for the most of them. The eight pesticides are resolved in less than 14 min.
Differential Pulse Voltammetric Determination of Local Anesthetics Heptacaine, Carbisocaine and Pentacaine at DNA Modified Screen‐Printed Electrode
Authors: Vaníčková M. , Jakubková E. , Bučková M. , Čižmárik J. , Labuda J.
Published: February 2004

A procedure for the differential pulse voltammetric determination of three local anesthetics (Heptacaine, Carbisocaine and Pentacaine) at a screen‐printed electrode surface modified with the dsDNA layer is described. The detection limits obtained after 120 s drug accumulation from 0.01 M phosphate buffer solution pH 6.96 are 0.02 μM (Pentacaine) and 0.03 μM (Carbisocaine and Heptacaine). The method was applied to the determination of Carbisocaine in spiked serum.
Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer
Authors: Bodiwala Dhaval , Luscombe Christopher J. , French Michael E. , Liu Samson , Saxby Mark F. , Jones Peter W. , Fryer Anthony A. , Strange Richard C.
Published: February 2004

Ultraviolet radiation (UVR) exposure may protect against prostate cancer development via a mechanism involving vitamin D. The vitamin D receptor (VDR) gene is therefore a candidate susceptibility factor for prostate cancer. This possibility has been previously investigated with conflicting results. We examined the association of VDR genotypes (variants at the CDX‐2, Fok1, and Taq1 sites), haplotypes, and genotype combinations with risk by studying 368 prostate cancer and 243 benign prostatic hypertrophy (BPH) patients. CDX‐2, Fok1, and Taq1 genotype and haplotype frequencies were not significantly different in cancer and BPH patients. As the impact of VDR polymorphisms may depend on UVR exposure, we studied associations of variants with risk in men stratified into low (below median) and high (above median) cumulative exposure/year groups. In men with UVR exposure above the median (1,100 hr/year), CDX‐2 GA and AA (odds ratios [OR] = 2.11 and 2.02, respectively) and Fok1 ff (OR = 2.91) were associated with increased prostate cancer risk. No associations were observed for Taq1 genotypes. Of the genotype combinations, relative to all other CDX‐2 and Taq1 and combinations, GGTT (P = 0.022, OR = 0.30), and relative to all other Fok1 and Taq1 combinations, FFTT (P = 0.026, OR = 0.35) were associated with reduced prostate cancer risk in the presence of the main effects. None of the other two‐ or three‐genotype combinations was associated with risk. These data indicate that VDR variants influence prostate cancer risk and that this association is dependent on the extent of UVR exposure. Environ. Mol. Mutagen. 43:121–127, 2004. © 2004 Wiley‐Liss, Inc.
Proteomic analysis of cellular responses to low concentration N‐methyl‐N′‐nitro‐N‐nitrosoguanidine in human amnion FL cells
Authors: Jin Jinghua , Yang Jun , Gao Zhihua , Yu Yingnian
Published: February 2004

We have shown previously that exposure to a low concentration of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) induces comprehensive changes in the protein expression profile of human amnion FL cells, including the induction, suppression, upregulation, and downregulation of various proteins. In addition, by proteomic analysis combining two‐dimensional gel electrophoresis (2‐DE) and mass spectrometry, some of the induced and suppressed proteins were identified. In this study, we identified an additional 18 proteins among those that were either up‐ or downregulated by MNNG treatment. The proteins identified were a heterogeneous group that included several zinc finger proteins, proteins involved in signal transduction, cytoskeletal proteins, cell‐cycle regulation proteins, and proteins with unknown functions. The involvement of these proteins in the cellular responses to alkylating agents has not been reported before and their physiological relevance is not clear. Therefore, our findings may help better understand the global cellular stress responses to chemical carcinogens, and may lead to new studies on the functions of these MNNG‐responsive proteins. Furthermore, some of these proteins may serve as biomarkers for detecting exposure of human populations to environmental carcinogens. Environ. Mol. Mutagen. 43:93–99, 2004. © 2004 Wiley‐Liss, Inc.