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

doi:10.1039/c0cc04937a

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 journal › Article (Academic Journal) › peer-review

20 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 language	English
Pages (from-to)	2517-2519
Number of pages	3
Journal	Chemical Communications
Volume	47
Issue number	9
DOIs	https://doi.org/10.1039/c0cc04937a
Publication status	Published - 2011

Keywords

FAAH INHIBITORS
IN-VIVO
SIMULATIONS
HYDROLYSIS
VARIANT

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COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE
Mulholland, A. J.
1/10/08 → 1/04/14
Project: Research

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Lodola, A., Capoferri, L., Rivara, S., Chudyk, E., Sirirak, J., Dyguda-Kazimierowicz, E., Sokalski, W. A., Mileni, M., Tarzia, G., Piomelli, D., Mor, M., & Mulholland, A. J. (2011). Understanding the role of carbamate reactivity in fatty acid amide hydrolase inhibition by QM/MM mechanistic modelling. Chemical Communications, 47(9), 2517-2519. https://doi.org/10.1039/c0cc04937a

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

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.",

keywords = "FAAH INHIBITORS, IN-VIVO, SIMULATIONS, HYDROLYSIS, VARIANT",

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

year = "2011",

doi = "10.1039/c0cc04937a",

language = "English",

volume = "47",

pages = "2517--2519",

journal = "Chemical Communications",

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publisher = "Royal Society of Chemistry",

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Lodola, A, Capoferri, L, Rivara, S, Chudyk, E, Sirirak, J, Dyguda-Kazimierowicz, E, Sokalski, WA, Mileni, M, Tarzia, G, Piomelli, D, Mor, M & Mulholland, AJ 2011, 'Understanding the role of carbamate reactivity in fatty acid amide hydrolase inhibition by QM/MM mechanistic modelling', Chemical Communications, vol. 47, no. 9, pp. 2517-2519. https://doi.org/10.1039/c0cc04937a

TY - JOUR

T1 - Understanding the role of carbamate reactivity in fatty acid amide hydrolase inhibition by QM/MM mechanistic modelling

AU - Lodola, Alessio

AU - Capoferri, Luigi

AU - Rivara, Silvia

AU - Chudyk, Ewa

AU - Sirirak, Jitnapa

AU - Dyguda-Kazimierowicz, Edyta

AU - Sokalski, W. Andrzej

AU - Mileni, Mauro

AU - Tarzia, Giorgio

AU - Piomelli, Daniele

AU - Mor, Marco

AU - Mulholland, Adrian J.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - FAAH INHIBITORS

KW - IN-VIVO

KW - SIMULATIONS

KW - HYDROLYSIS

KW - VARIANT

U2 - 10.1039/c0cc04937a

DO - 10.1039/c0cc04937a

M3 - Article (Academic Journal)

C2 - 21240393

SN - 1359-7345

VL - 47

SP - 2517

EP - 2519

JO - Chemical Communications

JF - Chemical Communications

IS - 9

ER -

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

Abstract

Keywords

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COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE

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