title: α-Carbonic Anhydrases Possess Thioesterase Activity.
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.
authors: 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.
authors: Muhammet
authors: M
authors: Tanc
authors: NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze , Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
authors: Fabrizio
authors: F
authors: Carta
authors: NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze , Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
authors: Andrea
authors: A
authors: Scozzafava
authors: 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.
authors: Claudiu T
authors: CT
authors: Supuran
keywords: Carbonic anhydrase; inhibitors; prodrugs; thioesterase