S-Arachidonoyl-2-thioglycerol synthesis and use for fluorimetric and colorimetric assays of monoacylglycerol lipase.
We report the first synthesis of 2-thioglycerol and S-arachidonoyl-2-thioglycerol (the thioester analog of the endocannabinoid 2-arachidonoylglycerol) in an eight or nine step procedure with a yield of approximately 25% and establish the use of this substrate for maleimide-based fluorescent and dithiobis(2-nitrobenzoic acid)-based colorimetric assays of human recombinant monoacylglycerol (MAG) lipase (hMAGL) and human brain membrane MAG hydrolase activity. Inhibitor structure-activity relationships observed here for hMAGL and 2-ATG correlate well (r(2)=0.93, n=9) with earlier findings for mouse brain MAG hydrolase with non-thiol substrates.
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. ectl@berkeley.edu
John E
JE
Casida
Alexander G
AG
Gulevich
Richmond
R
Sarpong
Eric M
EM
Bunnelle
D001095:Arachidonic Acids / Q000737:chemistry; D063385:Cannabinoid Receptor Modulators / Q000737:chemistry; D003124:Colorimetry; D063388:Endocannabinoids; D005470:Fluorometry; D005989:Glycerides / Q000737:chemistry; D006801:Humans; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050178:Monoglycerides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D050178:Monoglycerides; D011994:Recombinant Proteins; C549978:S-arachidonoyl-2-thioglycerol; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases