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

作者机构：Pingshan Translational Medicine CenterShenzhen Bay LaboratoryShenzhen 518118China State Key Laboratory of Chemical OncogenomicsSchool of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhen 518055 China Department of Breast and Thyroid SurgeryShenzhen People's HospitalShenzhen 518020China Department of Student AffairsBeihang UniversityBeijing 100191China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2021年第32卷第11期

页      面：3623-3626页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

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 

主　　题：Amino-yne reaction Progargylated sulfonium Proximity-induced MDM4 

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 *** report one example here that the propargylated-sulfonium center undergoes a nucleophilic reaction with lysine residue via proximity-induced *** propargylated-sulfonium tethered peptide resulting from a facile propargylation of thiolethers,enables amino-yne reaction at the selected lysine on MDM4 *** strategy represents a viable approach of lysine-targeted covalent inhibition in proximity.