Document Detail


The interaction of fatty acid amide hydrolase (FAAH) inhibitors with an anandamide carrier protein using (19)F-NMR.
MedLine Citation:
PMID:  23344792     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It has been reported that the endocannabinoid anandamide (AEA) binds to a class of fatty acid-binding proteins and serum albumin which can serve as carrier proteins and potentiate the cellular uptake of AEA and its intracellular translocation. Here, we employed (19)F nuclear magnetic resonance spectroscopy to study the interactions of serum albumin with two inhibitors of fatty acid amide hydrolase (FAAH), the enzyme involved in the deactivation of anandamide. We found that, for both inhibitors AM5206 and AM5207, the primary binding site on serum albumin is drug site 1 located at subdomain IIA. Neither inhibitor binds to drug site 2. While AM5207 binds exclusively to drug site 1, AM5206 also interacts with other fatty acid-binding sites on serum albumin. Additionally, AM5206 has an affinity for serum albumin approximately one order of magnitude higher than that of AM5207. The data suggest that interactions of FAAH inhibitors with albumin may provide added advantages for their ability to modulate endocannabinoid levels for a range of applications including analgesia, antiemesis, and neuroprotection.
Authors:
Jianqin Zhuang; De-Ping Yang; Spyros P Nikas; Jianhong Zhao; Jianxin Guo; Alexandros Makriyannis
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-24
Journal Detail:
Title:  The AAPS journal     Volume:  15     ISSN:  1550-7416     ISO Abbreviation:  AAPS J     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-10-22     Revised Date:  2014-01-26    
Medline Journal Info:
Nlm Unique ID:  101223209     Medline TA:  AAPS J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  477-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amidohydrolases / antagonists & inhibitors*
Arachidonic Acids / metabolism*
Binding Sites
Binding, Competitive
Carrier Proteins / metabolism*
Endocannabinoids / metabolism*
Enzyme Inhibitors / metabolism*,  pharmacology
Fluorine*
Ligands
Nuclear Magnetic Resonance, Biomolecular / methods*
Phenyl Ethers / metabolism*,  pharmacology
Polyunsaturated Alkamides / metabolism*
Protein Binding
Serum Albumin, Bovine / metabolism*
Grant Support
ID/Acronym/Agency:
DA003801/DA/NIDA NIH HHS; DA007215/DA/NIDA NIH HHS; DA007312/DA/NIDA NIH HHS; DA032020/DA/NIDA NIH HHS; R21 DA032020/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/AM 5206; 0/Arachidonic Acids; 0/Carrier Proteins; 0/Endocannabinoids; 0/Enzyme Inhibitors; 0/Ligands; 0/Phenyl Ethers; 0/Polyunsaturated Alkamides; 0/Serum Albumin, Bovine; 284SYP0193/Fluorine; 94421-68-8/anandamide; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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