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An E1‐Catalyzed Chemoenzymatic Strategy to Isopeptide‐ N ‐Ethylated Deubiquitylase‐Resistant Ubiquitin Probes
Author(s) -
Zheng Qingyun,
Wang Tian,
Chu GuoChao,
Zuo Chong,
Zhao Rui,
Sui Xin,
Ye Linzhi,
Yu Yuanyuan,
Chen Jingnan,
Wu Xiangwei,
Zhang Wenhao,
Deng Haiteng,
Shi Jing,
Pan Man,
Li YiMing,
Liu Lei
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202002974
Subject(s) - interactome , ubiquitin , chemistry , computational biology , biochemistry , combinatorial chemistry , biology , gene
Triazole‐based deubiquitylase (DUB)‐resistant ubiquitin (Ub) probes have recently emerged as effective tools for the discovery of Ub chain‐specific interactors in proteomic studies, but their structural diversity is limited. A new family of DUB‐resistant Ub probes is reported based on isopeptide‐ N ‐ethylated dimeric or polymeric Ub chains, which can be efficiently prepared by a one‐pot, ubiquitin‐activating enzyme (E1)‐catalyzed condensation reaction of recombinant Ub precursors to give various homotypic and even branched Ub probes at multi‐milligram scale. Proteomic studies using label‐free quantitative (LFQ) MS indicated that the isopeptide‐ N ‐ethylated Ub probes may complement the triazole‐based probes in the study of Ub interactome. Our study highlights the utility of modern protein synthetic chemistry to develop structurally and new families of tool molecules needed for proteomic studies.