转基因生物
基因工程
环肽
肽
噬菌体展示
肽库
生物
遗传学
计算生物学
肽序列
基因
生物化学
作者
Xiaoshan Shayna Wang,Peng‐Hsun Chase Chen,Joshua Trae Hampton,Jeffery M. Tharp,Catrina A. Reed,Saibal Das,Duen Shian Wang,Hamed S. Hayatshahi,Yang Shen,Jin Liu,Wenshe Ray Liu
标识
DOI:10.1002/anie.201908713
摘要
Abstract Superior to linear peptides in biological activities, cyclic peptides are considered to have great potential as therapeutic agents. To identify cyclic‐peptide ligands for therapeutic targets, phage‐displayed peptide libraries in which cyclization is achieved by the covalent conjugation of cysteines have been widely used. To resolve drawbacks related to cysteine conjugation, we have invented a phage‐display technique in which its displayed peptides are cyclized through a proximity‐driven Michael addition reaction between a cysteine and an amber‐codon‐encoded N ϵ ‐acryloyl‐lysine (AcrK). Using a randomized 6‐mer library in which peptides were cyclized at two ends through a cysteine–AcrK linker, we demonstrated the successful selection of potent ligands for TEV protease and HDAC8. All selected cyclic peptide ligands showed 4‐ to 6‐fold stronger affinity to their protein targets than their linear counterparts. We believe this approach will find broad applications in drug discovery.
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