Document Report Card

ID: ALA2069166

Journal: ACS Med Chem Lett

Title: β-Lactones Inhibit N-acylethanolamine Acid Amidase by S-Acylation of the Catalytic N-Terminal Cysteine.

Authors: Armirotti A, Romeo E, Ponzano S, Mengatto L, Dionisi M, Karacsonyi C, Bertozzi F, Garau G, Tarozzo G, Reggiani A, Bandiera T, Tarzia G, Mor M, Piomelli D.

Abstract: 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.

CiteXplore: 24900487

DOI: 10.1021/ml300056y