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-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 (r2 = 0.93, n = 9) with earlier findings for mouse brain MAG hydrolase with non-thiol substrates.

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