二肽基肽酶-Ⅳ抑制剂及其构效关系的研究进展

Structure activity relationship on dipeptidyl peptidase Ⅳ inhibitors:resarch advances

二肽基肽酶-Ⅳ(dipeptidyl peptidase Ⅳ,DPP-4)是经临床证实的治疗2型糖尿病的新靶点,近年来引起制药界的广泛关注。本文综述了几类主要的选择性DPP-4抑制剂及其构效关系的研究进展,特别是利用现有抑制剂-酶复合物晶体X线衍射研究得到的DPP-4结合位点的重要的结构信息,总结出抑制剂-酶紧密结合的重要分子间相互作用,为通过基于结构的药物设计来获得新型选择性DPP-4抑制剂提供依据。

Dipeptidyl peptidase IV （DPP-IV） is a clinically validated target for the treatment of type 2 diabetes and has received considerable interest from the pharmaceutical industry over the last years. In this review, we discuss the structural characteristics of the DPP-IV binding site and use the available X- ray information together with published structure-activity relationship data to identify the molecular inter- actions that are the most important for tight enzyme-inhibitor binding.