电泳剂
赖氨酸
化学
亲核细胞
共价键
胺气处理
半胱氨酸
组合化学
水解
蛋白质组
加合物
生物化学
氨基酸
酶
有机化学
催化作用
作者
Monika Raj,Kuei-Chien Tang,Jian Cao,Lisa Boatner,Linwei Li,Jonathan Farhi,K. N. Houk,Jennifer Spangle,Keriann M. Backus
标识
DOI:10.1002/anie.202112107
摘要
Abstract Proteome profiling by activated esters identified >9000 ligandable lysines but they are limited as covalent inhibitors due to poor hydrolytic stability. Here we report our efforts to design and discover a new series of tunable amine‐reactive electrophiles (TAREs) for selective and robust labeling of lysine. The major challenges in developing selective probes for lysine are the high nucleophilicity of cysteines and poor hydrolytic stability. Our work circumvents these challenges by a unique design of the TAREs that form stable adducts with lysine and on reaction with cysteine generate another reactive electrophiles for lysine. We highlight that TAREs exhibit substantially high hydrolytic stability as compared to the activated esters and are non‐cytotoxic thus have the potential to act as covalent ligands. We applied these alternative TAREs for the intracellular labeling of proteins in different cell lines, and for the selective identification of lysines in the human proteome on a global scale.
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