摘要:

AbstractThe new five‐volume Houben‐Weyl treatise on the Synthesis of Peptides and Peptidomimetics is reviewed and recommended. Copyright © 2003 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.534

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractThe progress made in a multidisciplinary research programme designed to elucidate the molecular basis of the interaction ofStaphylococcus aureussecreted autoinducing peptides (AIPs) with their respective cell surface receptors is reviewed. Copyright © 2003 European Peptide Society and John Wiley&Sons, Ltd

ISSN:1075-2617    

DOI:10.1002/psc.486

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractThe crystal‐state conformations of two octapeptides,pBrBz‐(D‐Iva)8‐OtBu (8I) and Ac‐[L‐(αMe)Val]8‐OH (8II), the heptapeptide Z‐[L‐(αMe)Val]7‐OH (7), the hexapeptide Z‐[L‐(αMe)Leu]6‐OtBu (6) and the tetrapeptide alkylamide Z‐(Aib)2‐L‐Glu(OMe)‐L‐Ala‐L‐Lol (5) were assessed by x‐ray diffraction analyses. Two independent molecules are observed in the asymmetric unit of eachL‐(αMe)Val homo‐peptide. All four homo‐peptides are folded in a regular 310‐helical structure (only theC‐terminal H‐bonded conformation of theD‐Iva octapeptide is distorted to a type‐I β‐turn). The hydroxyl groups of theC‐terminal carboxyl moieties of the twoL‐(αMe)Val homo‐peptides participate in an oxy‐analogue of the type‐III β‐turn conformation. While the twoL‐(αMe)Val 310‐helices are right‐handed, theD‐Iva andL‐(αMe)Leu helices are left‐handed. The tetrapeptide alkylamide is 310‐helical at theN‐terminus, but it is mixed 31

ISSN:1075-2617    

DOI:10.1002/psc.482

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractSyntheses are described of new dermorphin and [D‐Ala2]deltorphin I analogues in which the phenylalanine, the tyrosine or the valine residues have been substituted by the correspondingN‐alkyl‐glycine residues. Structural investigations by CD measurements in different solvents and preliminary pharmacological experiments were carried out on the resulting peptide–peptoid hybrids. The contribution from aromatic side chain residues is prominent in the CD spectra of dermorphin analogues and the assignment of a prevailing secondary structure could be questionable. In the CD spectra of deltorphin analogues the aromatic contribution is lower and the dichroic curves indicate the predominance of random conformer populations. The disappearance of the aromatic contribution in the [Ntyr1,D‐Ala2]‐deltorphin spectrum could be explained in terms of high conformational freedom of theN‐terminal residue. The kinetics of degradation of the synthetic peptoids digestion by rat and human plasma enzymes were compared with that of [Leu5]‐enkephalin. The binding to opioid receptors was tested on crude membrane preparations from CHO cells stably transfected with the µ‐ and δ‐opioid receptors. The biological potency of peptoids was compared with that of dermorphin in GPI preparations and with that of deltorphin I in MVD preparations. All the substitutions produced a dramatic decrease in the affinity of the peptide–peptoid hybrids for both the µ‐ and δ‐opioid receptors. Nval5and/or Nval6containing hybrids behaved as µ‐opioid receptor agonists and elicit a dose‐dependent analgesia (tail‐flick test) when injected i.c.v. in rats. Copyright © 2003 European Pep

ISSN:1075-2617    

DOI:10.1002/psc.487

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY

摘要:

AbstractA new family of cyclic opioid peptide analogues related to the 1–4 sequence of dermorphin/deltorphin (Tyr‐D‐Aaa2‐Phe‐Aaa4‐NH2) has been synthesized. The synthesis of the linear precursor peptides was accomplished by the solid‐phase method and ring formation was achieved via a ureido group incorporating the side chain amino functions ofD‐Aaa2(D‐Lys,D‐Orn) and Aaa4(Lys, Orn, Dab, Dap). The peptides were tested in the guinea‐pig ileum (GPI) and mouse vas deferens (MVD) assays. Most showed very high agonist potency in the GPI assay. The peptide containingD‐Lys in position 2 and Dab in position 4 was 210 times more active than enkephalin, and that containing Orn and Dab, respectively, was 150 times more active than enkephalin. The latter peptide was also very active in the MVD assay, and showed an IC50MVD/GPI ratio of 0.816. NMR spectra of selected peptides were recorded, and structural parameters were determined. The conformational space of the peptides was examined using the electrostatically driven Monte Carlo method. With the help of the NMR spectra each peptide was described as an ensemble of conformations. The conformations have been interpreted with regard to the opioid activities, and comparisons have been made with a model proposed earlier for enkephalin analogues. Copyright © 2003 European Peptide Society

ISSN:1075-2617    

DOI:10.1002/psc.510

出版商:John Wiley&Sons, Ltd.    

年代:2003

数据来源: WILEY