- Armirotti, Andrea;
- Romeo, Elisa;
- Ponzano, Stefano;
- Mengatto, Luisa;
- Dionisi, Mauro;
- Karacsonyi, Claudia;
- Bertozzi, Fabio;
- Garau, Gianpiero;
- Tarozzo, Glauco;
- Reggiani, Angelo;
- Bandiera, Tiziano;
- Tarzia, Giorgio;
- Mor, Marco;
- Piomelli, Daniele
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.