Peptide homologs, isosteres, and isomers: A general approach to structure–activity relationships
作者:
Murray Goodman,
期刊:
Biopolymers
(WILEY Available online 1985)
卷期:
Volume 24,
issue 1
页码: 137-155
ISSN:0006-3525
年代: 1985
DOI:10.1002/bip.360240112
出版商: Wiley Subscription Services, Inc., A Wiley Company
数据来源: WILEY
摘要:
AbstractA general approach to study peptide structure is presented using three areas of ongoing research in our laboratories. The first involves the molecular basis for taste of peptide derivatives. We synthesized dipeptides based onL‐aspartyl‐α‐aminocycloalkane carboxylic acid methyl ester. Ahomologousseries of cycloalkane derivatives was studied. The cyclopropane, cyclobutane, and cyclopentane derivatives are sweet, the cyclohexane and cycloheptane peptides are bitter, and the cyclooctane homolog is tasteless. The related acyclic analogL‐aspartyl‐aminoisobutyric acid methyl ester is sweet, while theL‐aspartyl diethyl glycine carboxylic acid methyl ester is tasteless. A model is presented to explain these experimental observations. The second area involves depsipeptides asisostericreplacements of α‐hydroxy acids for amino acid residues in peptide chains. We have synthesized sequentially defined polydepsipeptides as model systems for polypeptides. A detailed analysis of the conformational order for these polydepsipeptides is presented. The third area involves partial retro–inverso peptide modifications ofisomericcyclic enkephalin analogs, which illustrate the relationship between the modification and biological activity. We are probing the intramolecular hydrogen‐bonding features for these biologically active molecules. From such findings we are relating the structural and conformational preferences deduced from spectroscopy and molecular mechanics to
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