Understanding the role of carbamate reactivity in fatty acid amide hydrolase inhibition by QM/MM mechanistic modelling

Alessio Lodola*, Luigi Capoferri, Silvia Rivara, Ewa Chudyk, Jitnapa Sirirak, Edyta Dyguda-Kazimierowicz, W. Andrzej Sokalski, Mauro Mileni, Giorgio Tarzia, Daniele Piomelli, Marco Mor, Adrian J. Mulholland

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

18 Citations (Scopus)

Abstract

QM/MM modelling of FAAH inactivation by O-biphenyl-3-yl carbamates identifies the deprotonation of Ser241 as the key reaction step, explaining why FAAH is insensitive to the electron-donor effect of conjugated substituents; this may aid design of new inhibitors with improved selectivity and in vivo potency.

Original languageEnglish
Pages (from-to)2517-2519
Number of pages3
JournalChemical Communications
Volume47
Issue number9
DOIs
Publication statusPublished - 2011

Keywords

  • FAAH INHIBITORS
  • IN-VIVO
  • SIMULATIONS
  • HYDROLYSIS
  • VARIANT

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