【作者】 仇文卫； 徐杰； 李静雅； 李佳； 南发俊；

【Author】 Wen-Wei Qiu, Jie Xu, Jing-Ya Li, Jia Li*, Fa-Jun Nan* Chinese National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 201203, Shanghai

【机构】 中国科学院上海药物研究所国家新药筛选中心；

【Abstract】 Activity-based protein labeling by affinity chemical probes allows for a proteomic assessment of biochemical interactions, thereby providing comparative indices valuable for research and therapeutics. The utility of a chemical probe, including both specificity and affinity, largely relies on detail knowledge of targeted proteins and ability to synthesize ligands that are covalently active. Hence the challenge to satisfy these two concurrent requirements within one functional moiety often limits the scope of its general applicability. We rationalize that a modular separation of functional groups would be of advantageous. Here we report chemical strategy to synthesize a tri-modular photoaffinity labeling-CC probe (PAL-CC-ABP) with three functional groups for target recognition, proximal target cross-linking and distal reporter tag attachment. By testing a series of these probes for either recombinant or native methionine aminopeptidase and comparing with a conventional strategy, we demonstrate specificity, sensitivity, and the potential of general application of this tri-module strategy in both activity-based protein profiling and target identification of bioactive compounds.更多还原