α-碳酸酐酶具有硫酯酶活性。
α-Carbonic Anhydrases Possess Thioesterase Activity.
作者信息
Tanc Muhammet, Carta Fabrizio, Scozzafava Andrea, Supuran Claudiu T
机构信息
Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, Polo Scientifico , Room 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy ; NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze , Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze , Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
出版信息
ACS Med Chem Lett. 2015 Jan 19;6(3):292-5. doi: 10.1021/ml500470b. eCollection 2015 Mar 12.
Abstract
The α-carbonic anhydrases (CAs, EC 4.2.1.1) show catalytic versatility acting as esterases with carboxylic, sulfonic, and phosphate esters. Here we prove by kinetic, spectroscopic, and MS studies that they also possess thioesterase activity with a dithiocarbamate ester as a substrate (PhSO2NHCSSMe). Its CA-mediated hydrolysis leads to benzenesulfonamide, methyl mercaptan, and COS. The CA thioesterase activity may be useful for designing prodrug enzyme inhibitors, whereas some CA isoforms may use this activity for modulating physiologic/pathologic processes, which are possibly amenable to drug discovery of agents with multiple mechanisms of action.
摘要
α-碳酸酐酶（CAs，EC 4.2.1.1）具有催化多功能性，可作为羧酸酯酶、磺酸酯酶和磷酸酯酶发挥作用。在此，我们通过动力学、光谱学和质谱研究证明，它们还具有以二硫代氨基甲酸酯（PhSO2NHCSSMe）为底物的硫酯酶活性。其由CA介导的水解反应会生成苯磺酰胺、甲硫醇和COS。CA硫酯酶活性可能有助于设计前药酶抑制剂，而一些CA同工型可能利用这种活性来调节生理/病理过程，这可能有助于发现具有多种作用机制的药物。
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