Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.
Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Jinan, Shandong, China.
Med Res Rev. 2020 Mar;40(2):753-810. doi: 10.1002/med.21639. Epub 2019 Oct 9.
As a versatile therapeutic modality, peptides attract much attention because of their great binding affinity, low toxicity, and the capability of targeting traditionally "undruggable" protein surfaces. However, the deficiency of cell permeability and metabolic stability always limits the success of in vitro bioactive peptides as drug candidates. Peptide macrocyclization is one of the most established strategies to overcome these limitations. Over the past decades, more than 40 cyclic peptide drugs have been clinically approved, the vast majority of which are derived from natural products. The de novo discovered cyclic peptides on the basis of rational design and in vitro evolution, have also enabled the binding with targets for which nature provides no solutions. The current review summarizes different classes of cyclic peptides with diverse biological activities, and presents an overview of various approaches to develop cyclic peptide-based drug candidates, drawing upon series of examples to illustrate each strategy.
作为一种多功能的治疗模式，肽因其具有高结合亲和力、低毒性和靶向传统“不可成药”蛋白质表面的能力而备受关注。然而，细胞通透性和代谢稳定性的不足，始终限制了体外生物活性肽作为候选药物的成功。肽的环化是克服这些限制的最成熟策略之一。在过去的几十年中，已有 40 多种环肽药物在临床上获得批准，其中绝大多数来自天然产物。基于合理设计和体外进化发现的新型环肽，也能够与自然界无法提供解决方案的靶点结合。本文综述了具有不同生物活性的不同类型的环肽，并概述了开发基于环肽的候选药物的各种方法，通过一系列实例来说明每种策略。
