Université Paris 7 Denis Diderot, Université Sorbonne Paris Cité, Paris, France; UMRS 1160 Inserm, Paris, France; Centre d'Investigation Clinique 1427 Inserm/AP-HP Hôpital Saint Louis, Paris, France.
Université Paris-Sud, Laboratoire de Méthodologie, Synthèse et Molécules Thérapeutiques, ICMMO, UMR 8182, CNRS, Université Paris-Saclay, Faculté des Sciences d'Orsay, France.
Drug Discov Today. 2018 Feb;23(2):272-285. doi: 10.1016/j.drudis.2017.10.016. Epub 2017 Oct 31.
Protein-protein interactions (PPIs) are well recognized as promising therapeutic targets. Consequently, interfering peptides (IPs) - natural or synthetic peptides capable of interfering with PPIs - are receiving increasing attention. Given their physicochemical characteristics, IPs seem better suited than small molecules to interfere with the large surfaces implicated in PPIs. Progress on peptide administration, stability, biodelivery and safety are also encouraging the interest in peptide drug development. The concept of IPs has been validated for several PPIs, generating great expectations for their therapeutic potential. Here, we describe approaches and methods useful for IPs identification and in silico, physicochemical and biological-based strategies for their design and optimization. Selected promising in-vivo-validated examples are described and advantages, limitations and potential of IPs as therapeutic tools are discussed.
蛋白质-蛋白质相互作用（PPIs）被认为是很有前途的治疗靶点。因此，干扰肽（IPs）——能够干扰 PPIs 的天然或合成肽——越来越受到关注。鉴于其物理化学特性，与小分子相比，IPs 似乎更适合干扰涉及 PPIs 的大表面。在肽给药、稳定性、生物传递和安全性方面的进展也鼓励了人们对肽类药物开发的兴趣。干扰肽的概念已经在几种蛋白质-蛋白质相互作用中得到了验证，这为它们的治疗潜力带来了很高的期望。在这里，我们描述了用于识别干扰肽的方法和手段，以及基于计算机的、物理化学的和生物学的设计和优化策略。描述了一些经过体内验证的有前途的例子，并讨论了干扰肽作为治疗工具的优势、局限性和潜力。
