Assay and inhibition of diacylglycerol lipase activity.

New N-formyl-α-amino acid analogs of tetrahydrolipstatin (THL) were synthesized that inhibit human and murine diacylglycerol lipases. New reporter compounds were developed to screen inhibitors of 1,2-diacyl-sn-glycerol hydrolysis activity using fluorescence resonance energy transfer (FRET). Diacylglycerol lipase (DAGL) activities were quantified using [1″-14C]1-stearoyl-2-arachidonoyl-sn-glycerol substrate in a thin layer chromatography (TLC) assay using phosphorimaging analysis.