Chemical proteomics:terra incognita for novel drug target profiling

作     者：Fuqiang Huang Boya Zhang Shengtao Zhou Xia Zhao Ce Bian Yuquan Wei 

作者机构：The State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan 610041P.R.China Department of Gynecology and ObstetricsWest China Second HospitalSichuan UniversityChengduSichuan 610041P.R.China. 

出 版 物：《Chinese Journal of Cancer》 (Chinese Journal of Cancer)

年 卷 期：2012年第31卷第11期

页      面：507-518页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 1002[医学-临床医学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

基　　金：supported by grants from the National Basic Research Program of China (No.2011CB910703) the National 863 High Tech Foundation (No.2007AA021205) Chinese NSFC (No.81072022) 

主　　题：化学蛋白质组学 药物靶标 蛋白质相互作用 临床实践 药理作用 细胞成分 亲和层析 代谢途径 

摘      要：The growing demand for new therapeutic strategies in the medical and pharmaceutic fields has resulted in a pressing need for novel druggable targets.Paradoxically,however,the targets of certain drugs that are already widely used in clinical practice have largely not been annotated.Because the pharmacologic effects of a drug can only be appreciated when its interactions with cellular components are clearly delineated,an integrated deconvolution of drug-target interactions for each drug is necessary.The emerging field of chemical proteomics represents a powerful mass spectrometry(MS)-based affinity chromatography approach for identifying proteome-wide small molecule-protein interactions and mapping these interactions to signaling and metabolic pathways.This technique could comprehensively characterize drug targets,profile the toxicity of known drugs,and identify possible off-target activities.With the use of this technique,candidate drug molecules could be optimized,and predictable side effects might consequently be avoided.Herein,we provide a holistic overview of the major chemical proteomic approaches and highlight recent advances in this area as well as its potential applications in drug discovery.