摘要:

AbstractActivation of the platelet surface receptor GPIIb/IIIa is the final pathway of platelet aggregation, regardless of the initiating stimulus. RGD analogues, peptidomimetics and monoclonal antibodies to GPIIb/IIIa have been developed targeting the blockage of the receptor and inhibition of the fibrinogen binding. However, the intrinsic activating effect of GPIIb/IIIa blockers is widely discussed as one potential contributing factor for the disappointing outcome of trials with GPIIb/IIIa inhibitors. An alternative method for thrombus prevention could be the use of specific fibrinogen blockers since they will act at the final step of the platelet aggregation and are expected to leave the receptor unaffected. To achieve this target the design of the fibrinogen ligands could be based on (i) sequences derived from GPIIb/IIIa ligand binding sites, and (ii) sequences complementary to RGD and/or to fibrinogen γ‐chain. The available information, which could be used as a starting point for developing potent fibrinogen ligands, is reviewed. Copyright © 2004 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.603

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractA novel tool for polymer‐assisted solution phase (PASP) esterification of amino acid and peptide derivatives has been developed. When treated with carboxylic acids, polymer‐bound alkyltriazenes react with a loss of nitrogen and transfer of the alkyl moiety to the carboxylate anion to form the corresponding alkyl esters. There are no limitations with regard to either the protecting groups or the nature of the amino acid. Furthermore no racemization occurs at the chiral centers of the amino acids as demonstrated by chiral GC‐MS analyses. Alkyltriazene‐resins were also applied successfully to the esterification of peptide acids and other peptidic structures, such as tripalmitoyl‐S‐glyceryl‐cysteine (Pam3Cys). The triazene‐mediated esterification reaction is exceptionally mild, and there is no need for prior activation of the carboxy groups. This method is therefore particularly suitable for the alkylation of complex peptidomimetic structures prone to racemization and for acid‐sensitive structures. Copyright © 2004 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.581

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe conversion of soluble, nontoxic amyloid β‐protein (Aβ) to aggregated, toxic Aβ rich in β‐sheet structures is considered to be the key step in the development of Alzheimer's disease. Therefore, extensive studies have been carried out on the mechanisms involved in Aβ aggregation and the characterization of Aβ aggregates formed in aqueous solutions mimicking biological fluids. On the other hand, several investigators pointed out that membranes play an important role in Aβ aggregation. However, it remains unclear whether Aβ aggregates formed in solution and membranes are identical and whether the former can bind to membranes. In this study, using a dye‐labeled Aβ‐(1–40) as well as native Aβ‐(1–40), the properties of Aβ aggregates formed in buffer and raft‐like membranes composed of monosialoganglioside GM1/cholesterol/sphingomyelin were compared. Fourier transform infrared spectroscopic measurements suggested that Aβ aggregates formed in buffer and in membranes have different β‐sheet structures. Fluorescence experiments revealed that Aβ aggregated in buffer did not show any affinity for membranes. Copyright © 2004 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.570

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractThe synthetic octapeptide peptide T (ASTTTNYT) has been shown to interfere with binding of the HIV‐1 envelope glycoprotein gp120 to the chemokine receptor R5, thus preventing viral infection. This study investigated the degree of conformational order of two analogs of peptide T, one biologically active (D‐Ala peptide T amide) and one inactive (D‐Ala,D‐Tyr peptide T amide) using nuclear magnetic resonance (NMR) spectroscopy in an aqueous environment, both in solution and in the frozen solid state. Standard solution NMR techniques such as DQFCOSY, HMQC, ROESY and inversion recovery measurements have been utilized to characterize these peptides. Solid state NMR experiments were likewise employed to study the peptides in a frozen glycerol:water mixture. The NMR results indicate that the monomeric form of both peptide T analogs have considerable conformational heterogeneity. Solid state NMR studies indicate aggregation ofD‐Ala peptide T, possibly into a β‐sheet structure, at concentrations higher than 10 mM. Copyright © 2004 European Peptide Society and John Wi

ISSN:1075-2617    

DOI:10.1002/psc.571

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractHumanin is a novel, 24‐mer residue bioactive peptide, which antagonizes Alzheimer's disease (AD) related neurotoxicity and offers a hope for developing new therapeutics against AD. Access to adequate amounts of pure humanin is a prerequisite for further, thorough, investigation of the pharmacological properties and therapeutic potency of the peptide. Until now, humanin has been obtained mainly by molecular biology techniques. In this work the Fmoc solid‐phase synthesis of humanin on an in‐house prepared 2‐Cl‐tritylamidomethyl polystyrene resin is described fully. Special precautions, i.e. prolonged deprotection steps, should be taken to achieve a high overall yield, since humanin seems to contain a ‘difficult sequence’ (R4G5F6S7C8L9) near its highly lipophilic, biologically important region L9L10L11L12. Copyright © 2004 European Peptide Society and John W

ISSN:1075-2617    

DOI:10.1002/psc.572

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractHumanin and its analogues have been shown to protect cells against death induced by various Alzheimer's disease genes and amyloid‐β‐peptidesin vitro;the analogue [Gly14]‐humanin has also been shown to be potent in reversing learning and memory impairment induced by scopolamine in micein vivo. It is important to validate these results by using other behavioral methods. In this study, the effect of [Gly14]‐humanin and des‐Leu‐PAGA, another analogue (0.2 µmol kg−1, i.p.) on the 3‐quinuclidinyl benzilate‐induced (2 mg kg−1, i.p.) impairment of spatial memory in the multiple T‐maze in rats has been evaluated. Both peptides reversed the impairment of spatial memory. These results indicate the potential of humanin analogues in modulation of the cholinergic system. Copyright © 2004 European Peptide Society

ISSN:1075-2617    

DOI:10.1002/psc.569

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY