Deuterated and tritiated enantiomers of CP55,940 as novel probes of cannabinoid receptors

MEDI 32

Kejun Cheng, kejunch@niddk.nih.gov1, Klaus Gawrisch, klaus.gawrisch@hhs.gov2, and Kenner C. Rice, kr21f@nih.gov1. (1) Chemical Biology Research Branch, National Institute on Drug Abuse, National Institutes of Health, Building 8, Rm. B1-22, 8 Center Drive, MSC0815, Bethesda, MD 20892, (2) Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Rm. 3N-07, MSC9410, Bethesda, MD 20892
The peripheral type cannabinoid receptor (CB2) is a G-protein coupled receptor that is involved in numerous physiological processes and is therefore a potential target for medication development. Recenty, the functional human CB2 has been expressed in milligram quantities in E. coli, purified to over 80%, and reconstituted in a lipid matrix (artificial membrane) where it retained the expected drug binding properties. This presentation will describe our chemical and biological program to synthesize deuterated and tritiated enantiomers of the cannabinoid ligand CP55,940, and to utilize these probes to further characterize specific interactions of drugs with the CB2 binding pocket. The ligands initially targeted were (a) the tritiated inactive enantiomer (CP56,667) of CP55,940 for determination of nonspecific binding to the lipid matrix and differentiation from specific binding, and (b) CP55,940 containing the fully deuterated (D19) aromatic side chain as a probe to determine structure, location and dynamics of the specifically bound ligand by NMR and other methods.
 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007