The cysteine amidase N-acylethanolamine acid amidase (NAAA) is a member of the N-terminal nucleophile class of enzymes and a potential target for anti-inflammatory drugs. We investigated the mechanism of inhibition of human NAAA by substituted β-lactones. We characterized pharmacologically a representative member of this class, ARN077, and showed, using high-resolution liquid chromatography–tandem mass spectrometry, that this compound forms a thioester bond with the N-terminal catalytic cysteine in human NAAA.
β-Lactones Inhibit N-acylethanolamine Acid Amidase by S-Acylation of the Catalytic N-Terminal Cysteine / A. Armirotti; E. Romeo; S. Ponzano; L. Mengatto; M. Dionisi; C. Karacsonyi; F Bertozzi; G. Garau; G. Tarozzo; A. Reggiani; T. Bandiera; G. Tarzia; M. Mor; D. Piomelli. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 3(2012), pp. 422-426. [10.1021/ml300056y]
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