Proximity-induced amino-yne reaction for selective MDM4 conjugation via propargylated sulfonium  

作　　者：Chenshan Lian Yang Li Zhanfeng Hou Wanjin Zhong Ye Tian Feng Yin Zigang Li Dongxian Zhou Rui Wang 

机构地区：[1]Pingshan Translational Medicine Center,Shenzhen Bay Laboratory,Shenzhen 518118,China [2]State Key Laboratory of Chemical Oncogenomics,School of Chemical Biology and Biotechnology,Peking University Shenzhen Graduate School,Shenzhen 518055 China [3]Department of Breast and Thyroid Surgery,Shenzhen People's Hospital,Shenzhen 518020,China [4]Department of Student Affairs,Beihang University,Beijing 100191,China

出　　处：《Chinese Chemical Letters》2021年第11期3623-3626,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 Natural Science Foundation of China(Nos.21778009 and 21977010);the Natural Science Foundation ofGuangdongProvince(Nos.2020A1515010766,2020A1515010522,2019A1515111184 and 2019A1515110489);the Shenzhen Science and Technology Innovation Committee(Nos.JCYJ20180507181527112,JCYJ20180508152213145,and JCYJ20170817172023838);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 Proteomic Platform of Pingshan Translational Medicine Center;Shenzhen Bay Laboratory;the high-performance computing platform of Peking University.

摘　　要：Whilst most bioorthogonal reactions focus on targeting binding-site cysteine residues,proximity-induced reactivity effect ensures that reaction also occurs at nucleophilic lysine residues.We report one example here that the propargylated-sulfonium center undergoes a nucleophilic reaction with lysine residue via proximity-induced conjugation.This propargylated-sulfonium tethered peptide resulting from a facile propargylation of thiolethers,enables amino-yne reaction at the selected lysine on MDM4 protein.This strategy represents a viable approach of lysine-targeted covalent inhibition in proximity.

关 键 词：Amino-yne reaction Progargylated sulfonium Proximity-induced MDM4 

分 类 号：TQ460.1[化学工程—制药化工]