Photocaging of Activity‐Based Ubiquitin Probes via a C‐Terminal Backbone Modification Strategy

• DOI: 10.1002/anie.202203792
• Publication Date: 2022-04-23T08:11:11Z
• Authors: Yu Wang; Jingnan Chen; Xiao Hua; Xianbin Meng; Hongyi Cai; Rongtian Wang; Jing Shi; Haiteng Deng; Lei Liu; Yi‐Ming Li
• Keywords: Deubiquitinating enzyme

Photocaged, activity-based ubiquitin (Ub) probes (Ub-ABPs) have been developed for the time-resolved probing of deubiquitinating enzyme (DUB) activities, but many Ub-ABPs are still challenging to photocage because their warheads (e.g. propargylamide (PA) or dehydroalanine (Dha)) difficult temporally block and activate. Here, we describe a new C-terminal backbone modification strategy construction photocaged in which light-sensitive group is placed at amide bond Ub Gly75. This enabled facile generation cell-permeable Ub-PA Dha that could be activated capture DUBs after photo-irradiation, were used profile cells under specially designed conditions experiencing oxidative stress) with isopeptide linkage selectivity. anticipated provide general solution development ABPs bearing any DUB profiling.