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

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 ?-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.

SUBMITTER: Armirotti A 

PROVIDER: S-EPMC4025845 | biostudies-other | 2012 May

REPOSITORIES: biostudies-other

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

Armirotti Andrea A   Romeo Elisa E   Ponzano Stefano S   Mengatto Luisa L   Dionisi Mauro M   Karacsonyi Claudia C   Bertozzi Fabio F   Garau Gianpiero G   Tarozzo Glauco G   Reggiani Angelo A   Bandiera Tiziano T   Tarzia Giorgio G   Mor Marco M   Piomelli Daniele D  

ACS medicinal chemistry letters 20120406 5

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  ...[more]