Identification of Styryl Sulfonyl Fluoride as a Near-Perfect Michael Acceptor for Diversified Protein Bioconjugations  

作　　者：Qingsong Wu Qi Xue Ji Li Qinheng Zheng Xinlu Zhao Wannan Li Shiming Sun Wanxing Sha Yang Yang Yi Yang Jie P.Li 

机构地区：[1]State Key Laboratory of Coordination Chemistry,Chemistry and Biomedicine Innovation Center(ChemBIC),School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210093 [2]Cellular and Molecular Pharmacology,University of California San Francisco,San Francisco,CA 94143 [3]Glyco Therapy Biotechnology Co.,Ltd.,Qiantang Distirct,Hangzhou 310058

出　　处：《CCS Chemistry》2023年第10期2251-2263,共13页中国化学会会刊(英文)

基　　金：Financial support from the National Key R&D Program of China(grant no.2019YFA09006600);the National Natural Science Foundation of China(grant nos.21977048 and 92053111);the Natural Science Foundation of Jiangsu Province(grant no.BK20202004);the Beijing National Laboratory for Molecular Sciences(grant no.BNLMS20200);the Jiangsu Specially-Appointed Professor Plan,and the Program for Innovative Talents and Entrepreneur in Jiangsu is gratefully acknowledged.Q.Z.is the Connie and Bob Lurie Fellow of the Damon Runyon Cancer Research Foundation(DRG-2434-21).

摘　　要：Cysteine(Cys)-specific bioconjugation has widespread applications in the synthesis of protein conjugates,particularly for the functionalization of antibodies.Here,we report the discovery of transstyryl sulfonyl fluoride(SSF)as a near-perfect Michael acceptor for Cys-specific protein bioconjugation.Compared to maleimides,which are predominantly used,SSF exhibited better chemoselectivity,selfstability,and conjugate stability while maintaining comparable reactivity.Using SSF-derived probes,proteins can be readily modified on the Cys residue(s)to install functionalities,for example,fluorescent dyes,toxins,and oligonucleotides,without influencing the activity.Further applications of SSF-derived serum-stable antibody-drug conjugates and PD-L1 nanobody-oligo conjugates demonstrate the great translational value of SSF-based bioconjugation in drug development and single-cell sequencing.

关 键 词：styryl sulfonyl fluoride cysteine bioconjugation serum-stable ADC DNA-protein conjugates CITE-seq 

分 类 号：O62[理学—有机化学]