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

查看全文 作　　者：Hongkun [1]Xu;Xuan [1]Qin;Yaping [1]Zhang;Chuan [1]Wan;Rui [2]Wang;Zhanfeng [2]Hou;Xiaofeng [3]Ding;Hailing [1]Chen;Ziyuan [1,4]Zhou;Yang [1]Li;Chenshan [2]Lian;Feng [2]Yin;Zigang [1,2]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》索引2022年第33卷第4期,共4页 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