肽结构改造——药物开发的理想途径*

肽类化合物正逐渐成为开发新型药物先导化合物的重要来源。由于经典肽的结构在体内容易受到备种蛋白酶的作用而分解失活,且直链肽分子的柔曲性强,与受体结合的优势构象不突出,从而影响到与受体结合的选择性及活性强度。因此以经典肽为活性先导化合物进行结构改造成为开发新药的理想途径之一。现系统地归纳了活性肽如N-甲基肽、伪肽、末端改均肽、环肽、位点变构肽、娄肽、非天然肽、肽核酸、糖肽、拟肽、缀合肽等结构改造的类型,同时对一些代表性改构及活性情况分别予以介绍。

Structure modification of peptides: the rational way for drug development

Peptides are usually the original source of many lead compounds.However,its poor stability towards protein enzyme and insufficient receptor binding ability due to its flexible conformation limit its extensive application.Therefore,structure modification of classical peptide becomes a preferable way for drug research and development.Comprehensive strategies of peptide structure modification are classified systematically in present paper.Moreover,the structure features and bioactivity of some repre- sentative modified peptides such as N-methyl peptides,positional mutant peptides,peptoids unnatural peptides,PNA,glycopeptides,peptide mimetics,peptidyl-conjugates etc.are introduced respectively.