A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that Suppresses Inflammation and Human Macrophage Activation
| Autor: | Valeria Capurro, Luisa Mengatto, Giorgio Tarzia, Andrea Armirotti, Angelo Reggiani, Guillermo Moreno-Sanz, Silvia Pontis, Elisa Romeo, Valerio Chiurchiù, Fabio Bertozzi, Daniele Piomelli, Alison Ribeiro, Mauro Maccarrone, Tiziano Bandiera, Marco Mor, Andrea Nuzzi, Annalisa Fiasella |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Anti-Inflammatory Agents Inflammation Biology beta-Lactams Biochemistry Article Amidohydrolases Amidase chemistry.chemical_compound Oleoylethanolamide Hydrolase medicine Animals Humans Enzyme Inhibitors Receptor chemistry.chemical_classification Palmitoylethanolamide Macrophages General Medicine Macrophage Activation Mice Inbred C57BL Enzyme chemistry Molecular Medicine medicine.symptom Cysteine |
| Zdroj: | Ribeiro, A; Pontis, S; Mengatto, L; Armirotti, A; Chiurchiù, V; Capurro, V; et al.(2015). A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that Suppresses Inflammation and Human Macrophage Activation. ACS Chemical Biology, 10(8), 1838-1846. doi: 10.1021/acschembio.5b00114. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/53h085tr |
| ISSN: | 1554-8937 1554-8929 |
| DOI: | 10.1021/acschembio.5b00114 |
| Popis: | © 2015 American Chemical Society. Fatty acid ethanolamides such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are lipid-derived mediators that potently inhibit pain and inflammation by ligating type-α peroxisome proliferator-activated receptors (PPAR-α). These bioactive substances are preferentially degraded by the cysteine hydrolase, N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages. Here, we describe a new class of β-lactam derivatives that are potent, selective, and systemically active inhibitors of intracellular NAAA activity. The prototype of this class deactivates NAAA by covalently binding the enzymes catalytic cysteine and exerts profound anti-inflammatory effects in both mouse models and human macrophages. This agent may be used to probe the functions of NAAA in health and disease and as a starting point to discover better anti-inflammatory drugs. |
| Databáze: | OpenAIRE |
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