This proposal evaluates the hypothesis that N-(3-hydroxyphenyl)arachidonylamide (3-HPA) is a selective, mechanism-based inactivator of COX-2. COX-2 has important implications in inflammatory processes, cancer, and endocannabinoid metabolism. Metabolism of 3-HPA by COX-1 and COX-2 may provide insight into selectivity of endocannabinoid oxygenation, as well as the selectivity of COX-2 inactivation by 3-HPA. This will involve product characterization by tandem mass spectrometry and structure determination by x-ray crystallography. 3-HPA also represents the first metabolism-dependent, selective inactivator of COX-2. Quantification of 3-HPA oxidation by high performance liquid chromatography with UV detection, analysis of protein inactivation by thin layer chromatography, and determination of the site of modification by proteomic approaches involving electrospray ionization mass spectrometry will be important in characterizing the mechanism of inactivation. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA021014-01
Application #
7055927
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Babecki, Beth
Project Start
2006-05-01
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
1
Fiscal Year
2006
Total Cost
$37,082
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212