Crystalline form of fatty acid amine hydrolase (faah)

Details Crystalline form of fatty acid amine hydrolase (faah) Crystalline form of fatty acid amine hydrolase (faah)

C - Chemistry, Metallurgy

12

N

C12N 9/80 (2006.01) A61K 45/00 (2006.01) C12N 9/78 (2006.01) C12N 15/09 (2006.01) G01N 23/20 (2006.01) G06F 19/00 (2006.01)

Patent

CA 2506026

The present invention is directed to FAAH crystals in complex with the inhibitor methoxyarachidonyl fluorophosphonate (MAFP) and to the use of these crystals to determine the three-dimensional structure of FAAH. This invention id further directed to the use of this structure for the modeling or determination of the structures of related proteins. This invention is further directed to the use of this structure in the pursuit of drug design to identify, characterize, or optimize agents which bind to the active site, substrate channels, product channels, or regulatory sites of FAAH, and to the evaluation of these agents to identify agents which may stimulate, inhibit, relocalize, stabilize, or destabilize FAAH and/or its activity. This invention is further directed to the use of this structure in the development of engineered FAAH variants which display altered solubility, catalytic profiles, or substrate specificity. This invention is further directed to the use of this structure in the development of engineered heterologous proteins with altered membrane tropism.

La présente invention concerne des cristaux de FAAH formant un complexe avec l'inhibiteur de méthoxyarachidonyl fluorophosphonate (MAFP) et l'utilisation de ces cristaux pour déterminer la structure tridimensionnelle de FAAH. L'invention concerne également l'utilisation de cette structure pour modéliser ou déterminer les structures de protéines liées. L'invention concerne également l'utilisation de cette structure pour poursuivre le développement de médicaments pour identifier, caractériser ou optimiser des agents qui se lient au site actif, canaux substrat, canaux produit ou sites de régulation de FAAH et l'évaluation de ces agents pour identifier les agents qui peuvent stimuler, inhiber, relocaliser, stabiliser ou déstabiliser le FAAH et/ou son activité. L'invention concerne également l'utilisation de cette structure pour développer des variantes de FAAH affichant une solubilité, des profils catalytiques ou une spécificité de substrat modifiés. Cette invention concerne également l'utilisation de cette structure pour développer des protéines hétérologues au tropisme de membrane modifié mises en oeuvres

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