Spontaneous, co-translational peptide macrocyclization using p -cyanoacetylene–phenylalanine
Spontaneous, co-translational peptide macrocyclization using p -cyanoacetylene–phenylalanine
复制标题
使用对氰基乙炔苯丙氨酸进行自发共翻译肽大环化
DOI：
10.1039/d2cc01148d
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发表时间：
2022
影响因子：
4.9
通讯作者：
Hartman, Matthew C.
中科院分区：
文献类型：
--
作者：
Franco, H. Estheban;Chaloux, Brennan T.;Hartman, Matthew C.
肽大环化合物 (PMC) 在蛋白质-蛋白质相互作用 (PPI) 抑制剂的开发中越来越受欢迎。使用 mRNA 展示和噬菌体展示等展示技术可以访问大型 PMC 文库。这些技术要求大环化化学物质与生物环境相容，严重限制了可用于环化的技术类型。在这里，我们介绍了新型非规范氨基酸（ncAA）对氰基乙炔-L-Phe（pCAF），它在生理条件下通过与半胱氨酸的迈克尔加成促进自发的共翻译环化。这种新的、强大的化学反应可产生各种环尺寸的稳定大环，包括双环结构。
Peptide macrocycles (PMCs) are increasingly popular for the development of inhibitors of protein–protein interactions (PPIs). Large libraries of PMCs are accessible using display technologies like mRNA display and phage display. These technologies require macrocyclization chemistries to be compatible with biological milieu, severely limiting the types of technologies available for cyclization. Here, we introduce the novel non-canonical amino acid (ncAA) p-cyanoacetylene–L-Phe (pCAF), which facilitates spontaneous, co-translational cyclization through Michael addition with cysteine under physiological conditions. This new, robust chemistry creates stable macrocycles of a wide variety of ring sizes including bicyclic structures.