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 ∼25% and establish the use of this substrate for maleimide-based fluorescent and dithiobis(2-nitro...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2010-03, Vol.18 (5), p.1942-1947
Main Authors: Casida, John E., Gulevich, Alexander G., Sarpong, Richmond, Bunnelle, Eric M.
Format: Article
Language:English
Subjects:
2-Arachidonoyl glycerol
Arachidonic Acids - chemistry
Cannabinoid Receptor Modulators - chemistry
Colorimetry
Endocannabinoid
Endocannabinoids
Fluorometry
Glycerides - chemistry
Humans
Monoacylglycerol lipase
Monoacylglycerol Lipases - antagonists & inhibitors
Monoacylglycerol Lipases - genetics
Monoacylglycerol Lipases - metabolism
Monoglycerides - chemical synthesis
Monoglycerides - chemistry
Monoglycerides - metabolism
Recombinant Proteins - antagonists & inhibitors
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
S-Arachidonoyl-2-thioglycerol
Structure-Activity Relationship
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Summary: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 ∼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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2010.01.034