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Interfering peptides targeting protein–protein interactions: the next generation of drugs?
Drug Discovery Today ( IF 7.4 ) Pub Date : 2017-10-31 , DOI: 10.1016/j.drudis.2017.10.016
Heriberto Bruzzoni-Giovanelli , Valerie Alezra , Nicolas Wolff , Chang-Zhi Dong , Pierre Tuffery , Angelita Rebollo

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.



中文翻译:

靶向蛋白质间相互作用的干扰肽:下一代药物?

蛋白质间相互作用(PPI)被公认为有希望的治疗靶标。因此,干扰肽(IP)–能够干扰PPI的天然或合成肽–受到越来越多的关注。鉴于其理化特性,IP似乎比小分子更适合干扰PPI涉及的大表面。肽管理,稳定性,生物传递性和安全性方面的进展也鼓励了人们对肽药物开发的兴趣。IP的概念已针对多种PPI进行了验证,对其治疗潜力产生了很高的期望。在这里,我们描述了可用于IP识别的方法和方法,以及用于其设计和优化的计算机,物理化学和基于生物学的策略。选择有前途的描述了体内验证的实例,并讨论了IP作为治疗工具的优点,局限性和潜力。

更新日期:2017-10-31
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