摘要:

AbstractThe family of G protein‐coupled receptors constitutes about 50% of the therapeutic drug targets used in clinical medicine today, although the mechanisms of ligand binding, activation and signal transduction for G protein‐coupled receptors are not yet well defined. This review discusses ongoing research using the photoaffinity scanning method to map the bimolecular interface between class II G protein‐coupled receptors and their ligands. Furthermore the available computer model of class II peptide ligand docking into the receptor, based on the positional constraints imposed by the photoaffinity scanning analyses, will be discussed briefly. The ultimate goal of these efforts is to understand the molecular basis of receptor binding and therefore to generate a template for rational drug design. Copyright © 2003 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.541

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractIn our previous study, HP(2–9)‐MA(1–12), HP‐MA for short, a hybrid peptide incorporating residues 2–9 ofHelicobacter pyloriribosomal protein L1 (HP) and residues 1–12 of magainin 2 (MA) was shown to have strong antibacterial activity. In this study the antifungal activity of HP‐MA was evaluated using various fungi, and it was shown that the activity was increased when compared with the parent peptides. In order to investigate the fungicidal mechanism(s) of HP‐MA its action against fungal cell membranes was examined by the potassium‐release test, which showed that HP‐MA caused an increase in the amount of K+released from the cells. Furthermore, HP‐MA induced significant morphological changes. These facts suggested that the fungicidal effect of HP‐MA involves damaging the fungal cell membranes. CD investigators suggested that the α‐helical structure of these peptides plays an important role in their antibiotic effect, but that α‐helicity is less directly correlated with the enhanced antibiotic activity of the hybrid. Copyright © 2003 European Peptide So

ISSN:1075-2617    

DOI:10.1002/psc.489

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractAggregated amyloid β‐peptide (Aβ) is the primary constituent of the extracellular plaques and perivascular amyloid deposits associated with Alzheimer's disease (AD). Deposition of the cerebral amyloid plaques is thought to be central to the disease progression. One such molecule that has previously been shown to ‘dissolve’ deposited amyloid in post‐mortem brain tissue is bathocuproine (BC). In this paper1H NMR chemical shift analysis and pulsed field gradient NMR diffusion measurements were used to study BC self‐association and subsequent binding to Aβ. The results show that BC undergoes self‐association as its concentration increases. The association constant of BC dimerization,Ka, was estimated to be 0.64 mM−1at 25°C from1H chemical shift analysis. It was also found that dimerization of BC appeared to be essential for its binding to Aβ. From the self‐association constant of BC,Ka, the fraction of dimeric BC in the complex was obtained and the dissociation constant,Kd, of BC bound to Aβ40 peptide was then determined to be ∼1 mM. Copyright © 2003 European Peptide Society

ISSN:1075-2617    

DOI:10.1002/psc.539

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY

摘要:

AbstractCyclotetrapeptides are constrained cyclic peptides whose synthesis is considered a difficult task. A methodology based on on‐resin head‐to‐tail cyclization by anchoring the side chain of a trifunctional amino acid was investigated. A series of model cyclotetrapeptides containing the RGD sequence cyclo(Xaa‐Arg‐Gly‐Asp) (Xaa = Ala, Phe, Phg,D‐Ala,D‐Phe,D‐Phg) was synthesized with no cyclodimerization by‐products. An evaluation and optimization study of all of the parameters directly involved in the ring closure was performed. Copyright © 2003 European Peptide Society and

ISSN:1075-2617    

DOI:10.1002/psc.512

出版商:John Wiley&Sons, Ltd.    

年代:2004

数据来源: WILEY