1: Amino Acids. 2008 Jan;34(1):127-33. Epub 2007 May 4.

A MBP-FAAH fusion protein as a tool to produce human and rat fatty acid amide
hydrolase: expression and pharmacological comparison.

Labar G, Vliet FV, Wouters J, Lambert DM.

Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculté 
de Médecine, Université catholique de Louvain, Bruxelles, Belgium.

Fatty acid amide hydrolase (FAAH), a membrane-anchored enzyme responsible for the
termination of endocannabinoid signalling, is an attractive target for treating
conditions such as pain and anxiety. Inhibitors of the enzyme, optimized using
rodent FAAH, are known but their pharmacology and medicinal chemistry properties 
on the human FAAH are missing. Therefore recombinant human enzyme would represent
a powerful tool to evaluate new drug candidates. However, the production of high 
amounts of enzyme is hampered by the known refractiveness of FAAH to
overexpression. Here, we report the successful overexpression of rat and human
FAAH as a fusion to the E. coli maltose-binding protein, retaining catalytic
properties of native FAAH. Several known FAAH inhibitors were tested and
differences in their potencies toward the human and rat FAAH were found,
underscoring the importance of using a human FAAH in the development of
inhibitors.


PMID: 17476568 [PubMed - indexed for MEDLINE]

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