Kee K Suat, Jois Seetharama D S
Department of Pharmacy, 18 Science drive 4, National University of Singapore, Singapore 117543.
Curr Pharm Des. 2003;9(15):1209-24. doi: 10.2174/1381612033454900.
Peptides and proteins are essential to many biological processes. The interaction between the peptide ligands and their receptor targets commonly involves beta-turn structures. Yet poor bioavailability and unfavorable pharmacokinetics significantly compromise the use of peptides as drugs. Thus, there has been a great deal of interest in the design of peptidomimetics (modified peptides) as therapeutic agents by mimicking beta-turn structures. This review highlights the importance of beta-turn in the design of various peptidomimetics for many diseases. This review also outlines several beta-turn mimicking strategies and its application in the design of potent peptide analogues. beta-turn mimetics often tend to be more rigid in positioning the critically important amino acid residues and thus optimize the surface conformation for productive interaction with the receptors.
肽和蛋白质对许多生物过程至关重要。肽配体与其受体靶点之间的相互作用通常涉及β-转角结构。然而，较差的生物利用度和不利的药代动力学严重影响了肽作为药物的应用。因此，通过模拟β-转角结构来设计肽模拟物（修饰肽）作为治疗剂引起了广泛关注。本综述强调了β-转角在多种疾病的各种肽模拟物设计中的重要性。本综述还概述了几种模拟β-转角的策略及其在强效肽类似物设计中的应用。β-转角模拟物在定位至关重要的氨基酸残基时往往更具刚性，从而优化表面构象以与受体进行有效相互作用。
