An activity-based probe developed by a sequential dehydroalanine formation strategy targets HECT E3 ubiquitin ligases

作者：Ling Xu, Jian Fan, Yu Wang, Zhongping Zhang, Yao Fu, Yi‐Ming Li, Jing Shi · 发表于：Chemical Communications · 年份：2019 · DOI：10.1039/c9cc03739j · 被引用次数：36 · 研究领域：Ubiquitin and proteasome pathways、Protein Degradation and Inhibitors、Peptidase Inhibition and Analysis

E3 ligases play a critical role in ubiquitin (Ub) conjugation cascades, and any aberration in their activity is associated with a number of diseases. Advancement in our knowledge of understanding the roles of HECT E3s requires biochemical tools such as activity-based probes (ABPs). In this study we developed a novel dehydroalanine (Dha)-based E2-Ub ABP using a strategy that is a combination of practical hydrazide-based native chemical ligation and sequential Dha formation. The probe could be used for labeling HECT E3s not only in vitro but also in endogenous cellular contexts. Our easy-to-implement method is expected to be useful for the preparation of Dha based Ub family E2 conjugate ABPs.