基于活性和基于亲和性的蛋白质表达谱在药理毒理学研究中的应用进展  

Applications of activity-based protein profiling and affinity-based protein profiling in pharmacology and toxicology research

作　　者：陈佳胜 张鑫月 刘俊宏 孟文琪 张玲 CHEN Jiasheng;ZHANG Xinyue;LIU Junhong;MENG Wenqi;ZHANG Ling(School of Pharmacy,Xuzhou Medical University,Xuzhou 221004,China;Department of Naval Medicine,Naval Medical University,Shanghai 200433,China)

机构地区：[1]徐州医科大学药学院,江苏徐州221004 [2]海军军医大学海军医学系,上海200433

出　　处：《中国药理学与毒理学杂志》2023年第12期951-958,共8页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(82271916);国家自然科学基金(81801869)。

摘　　要：基于活性的蛋白质表达谱(ABPP)和基于亲和性的蛋白质表达谱(AfBPP)分析技术是以化合物为中心的化学蛋白质组学技术,在鉴定小分子药物和(或)毒物的直接作用靶点方面具有显著优势。明确直接作用靶点有助于更加全面地认识小分子化合物的药理毒理机制。本文简要介绍ABPP和AfBPP技术,并总结了近年来该技术在药物脱靶、毒物靶点鉴定方面的应用实例,如克雷诺拉尼、BIA 10-2474和奥利司他等药物的脱靶效应及VX、杀螟硫磷和丙烯醛等有毒化合物的直接作用靶点鉴定,以期对药理学、毒理学和化学生物学研究有一定的启发和借鉴意义。Activity-based protein profiling(ABPP)and affinity-based protein profiling(AfBPP)are reliable chemical proteomics techniques that exhibit significant advantages in identifying the direct acting targets of small molecule drugs and toxicants,which can help researchers understand the pharmaco⁃logical and toxicological mechanisms of active small molecules.This paper introduces ABPP and AfBPP technologies and summarizes the applications of this technique in drug off-target effect and target iden⁃tification of toxicants in recent years,such as drug off-target effect of crenolanib,BIA 10-2474,orlistat and target identification of VX,fenitrothion,acrolein.It is hoped that this review will give readers a better idea of ABPP/AfBPP and offer a line of thinking for researchers in the fields of pharmacology,toxicology and chemical biology.

关 键 词：基于活性的蛋白质表达谱 基于亲和性的蛋白质表达谱 靶标鉴定 药物脱靶效应 毒性化合物 

分 类 号：R96[医药卫生—药理学] R99[医药卫生—药学]