Biocompatible and Rapid Cyclization of Peptides with 2,4-Difluoro-6-hydroxy-1,3,5-benzenetricarbonitrile for the Development of Cyclic Peptide Libraries
Biocompatible and Rapid Cyclization of Peptides with 2,4-Difluoro-6-hydroxy-1,3,5-benzenetricarbonitrile for the Development of Cyclic Peptide Libraries
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使用 2,4-二氟-6-羟基-1,3,5-苯三甲腈对肽进行生物相容性快速环化，用于开发环肽文库
DOI：
10.1021/acs.bioconjchem.0c00363
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发表时间：
2020-09-01
影响因子：
4.7
通讯作者：
Wu, Chuanliu
中科院分区：
文献类型：
--
作者：
Zheng, Xuejun;Liu, Weidong;Wu, Chuanliu
我们报道了半胱氨酸硫醇与2,4 - 二氟 - 6 - 羟基 - 1,3,5 - 苯三甲腈（DFB）之间具有生物相容性的快速反应，该反应能够在中性水溶液中实现肽的高效环化。该反应进一步应用于环化噬菌体表面展示的肽，且不降低噬菌体的感染性，从而提供了可用于筛选环肽配体的高质量环肽文库。利用DFB - 环肽文库，我们鉴定出了能够区分促存活蛋白Bcl - xl及其近亲Bcl - 2的配体。因此，本研究一方面报道了一种用于构建环肽文库的有用反应，另一方面为进一步设计选择性Bcl - xl配体提供了有价值的线索。
We report a biocompatible and rapid reaction between cysteine thiols and 2,4-difluoro-6-hydroxy-1,3,5-benzenetricarbonitrile (DFB), which enables the efficient cyclization of peptides in neutral aqueous solutions. The reaction was further applied to cyclize peptides displayed on the phage surface without reducing phage infectivity, thus affording high-quality cyclic peptide libraries useful for screening of cyclic peptide ligands. Using the DFB-cyclic peptide library, we identified ligands that can distinguish the pro-survival protein Bcl-xl from its close relative Bcl-2. Therefore, this study on one hand reports a useful reaction for the construction of cyclic peptide libraries, and on the other hand presents valuable hits for further design of selective Bcl-xl ligands.