尾-Lactones Inhibit N-acylethanolamine Acid Amidase by S-Acylation of the Catalytic N-Terminal Cysteine
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- 作者：Andrea Armirotti ; Elisa Romeo ; Stefano Ponzano ; Luisa Mengatto ; Mauro Dionisi ; Claudia Karacsonyi ; Fabio Bertozzi ; Gianpiero Garau ; Glauco Tarozzo ; Angelo Reggiani ; Tiziano Bandiera ; Giorgio Tarzia ; Marco Mor ; Daniele Piomelli
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：May 10, 2012
- 年：2012
- 卷：3
- 期：5
- 页码：422-426
- 全文大小：281K
- 年卷期：v.3,no.5(May 10, 2012)
- ISSN：1948-5875
文摘
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 尾-lactones. We characterized pharmacologically a representative member of this class, ARN077, and showed, using high-resolution liquid chromatography鈥搕andem mass spectrometry, that this compound forms a thioester bond with the N-terminal catalytic cysteine in human NAAA.