A bifunctional vinyl-sulfonium tethered peptide induced by thio-Michael-type addition reaction  

作　　者：Hongkun Xu Xuan Qin Yaping Zhang Chuan Wan Rui Wang Zhanfeng Hou Xiaofeng Ding Hailing Chen Ziyuan Zhou Yang Li Chenshan Lian Feng Yin Zigang Li 

机构地区：[1]State Key Laboratory of Chemical Oncogenomics,School of Chemical Biology and Biotechnology,Peking University Shenzhen Graduate School,Shenzhen 518055,China [2]Pingshan translational medicine center,Shenzhen Bay Laboratory,Shenzhen 518055,China [3]Anhui Medical University,Hefei 230032,China [4]Cancer Hospital Chinese Academy of Medical Sciences,Shenzhen Center,Shenzhen 518000,China

出　　处：《Chinese Chemical Letters》2022年第4期2001-2004,共4页中国化学快报（英文版）

基　　金：financial support from the National Key Research and Development Program"Synthetic Biology"Key Special Project of China (No. 2018YFA0902504);the China Postdoctoral Science Foundation (No. 2021M690220);the National Natural Science Foundation of China (Nos. 21778009 and21977010);the Natural Science Foundation of Guangdong Province(Nos. 2019A1515110487, 2020A1515010522 and 2019A1515111184);the Shenzhen Science and Technology Innovation Committee (Nos. JCYJ20180507181527112, JCYJ20180508152213145, and JCYJ20170817172023838);the Foundation for Basic and Applied Research of Guangdong Province (No. 2019A1515110489);Guangdong Medical Science Foundation (No. A2021413);financial support from Beijing National Laboratory of Molecular Science Open Grant (No. BNLMS20160112);Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions (No. 2019SHIBS0004);supported by the high-performance computing platform of Peking University。

摘　　要：The modification and functionalization of peptides is of great significance in modern biotechnology and drug development. Here we report a highly reactive Michael-type warhead for the covalently modification of cysteine on peptide and protein. By installing a vinyl group onto a methionine residue of peptide,the produced vinyl sulfonium can be efficiently nucleophilic added by appropriate cysteine residue of this peptide, and thus yield a cyclized peptide. This peptide cyclization strategy was proven to exhibit improved cell penetration and good stability. Moreover, a peptide ligand bearing vinyl sulfonium could covalently bind to the cysteine in the target protein, indicating the potential of vinyl sulfonium as a novel warhead for developing covalent peptide inhibitor.

关 键 词：Vinyl sulfonium Michael-type addition Peptide cyclization Covalent peptide inhibitor Proximity-induced ligation 

分 类 号：TQ464.7[化学工程—制药化工]