Analytical methodologies for sensing catechol-O-methyltransferase activity and their applications  

作　　者：Fang-Yuan Wang Ping Wang Dong-Fang Zhao Frank J.Gonzalez Yu-Fan Fan Yang-Liu Xia Guang-Bo Ge Ling Yang 

机构地区：[1]Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,201203,China [2]School of Life Science and Medicine,Dalian University of Technology,Panjin,124221,China [3]Laboratory of Metabolism,Center for Cancer Research,National Cancer Institute,National Institutes of Health,Bethesda,MD,USA

出　　处：《Journal of Pharmaceutical Analysis》2021年第1期15-27,共13页药物分析学报（英文版）

基　　金：supported by the National Key Research and Development Program of China(2017YFC1700200,2017YFC1702000),the National Natural Science Foundation of China(81922070,81703604,81973286,81773687 and 81603187);Natural Science Foundation of Shanghai(18ZR1436500);Program of Shanghai Academic/Technology Research Leader(18XD1403600);Shuguang Program(18SG40)supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission;the project sponsored by the development fund for Shanghai talents(2019);the Key Science and Technology Program of Shenyang supported by Shenyang Science and Technology Bureau(17-230-9-05).

摘　　要：Mammalian catechol-O-methyltransferases(COMT)are an important class of conjugative enzymes,which play a key role in the metabolism and inactivation of catechol neurotransmitters,catechol estrogens and a wide range of endobiotics and xenobiotics that bear the catechol group.Currently,COMT inhibitors are used in combination with levodopa for the treatment of Parkinson’s disease in clinical practice.The crucial role of COMT in human health has raised great interest in the development of more practical assays for highly selective and sensitive detection of COMT activity in real samples,as well as for rapid screening and characterization of COMT inhibitors as drug candidates.This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications.Several lists of biochemical assays for measuring COMT activity,including the probe substrates,along with their analytical conditions and kinetic parameters,are presented.Finally,the challenges and future perspectives in the field,such as visualization of COMT activity in vivo and in situ,are highlighted.Collectively,this review article overviews the practical assays for measuring COMT activities in complex biological samples,which will strongly facilitate the investigations on the relevance of COMT to human diseases and promote the discovery of COMT inhibitors via high-throughput screening.

关 键 词：Catechol-O-Methyltransferase(COMT) Enzymatic activity Probe substrate COMT inhibitor High-throughput screening 

分 类 号：R446[医药卫生—诊断学]