CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Department of Chemistry, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2819-516 Caparica, Portugal.
CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
Drug Discov Today. 2022 Oct;27(10):103328. doi: 10.1016/j.drudis.2022.07.013. Epub 2022 Jul 27.
Catechol-O-methyltransferase (COMT) is an enzyme responsible for the O-methylation of biologically active catechol-based molecules. It has been associated with several neurological disorders, especially Parkinson's disease (PD), because of its involvement in catecholamine metabolism, and has been considered an important therapeutic target for central nervous system disorders. In this review, we summarize the biophysical, structural, and therapeutical relevance of COMT; the medicinal chemistry behind the development of COMT inhibitors and the application of computer-aided design to support the design of novel molecules; current methodologies for the biosynthesis, isolation, and purification of COMT; and revise existing bioanalytical approaches for the assessment of enzymatic activity in several biological matrices.
儿茶酚-O-甲基转移酶（COMT）是一种负责生物活性儿茶酚类分子 O-甲基化的酶。由于其参与儿茶酚胺代谢，它与几种神经退行性疾病有关，尤其是帕金森病（PD），并被认为是中枢神经系统疾病的重要治疗靶点。在这篇综述中，我们总结了 COMT 的生物物理、结构和治疗相关性；开发 COMT 抑制剂背后的药物化学以及计算机辅助设计在支持新型分子设计中的应用；COMT 的生物合成、分离和纯化的当前方法；并修订了现有的生物分析方法，以评估几种生物基质中酶活性。
