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Updated: Feb 7, 2026

Defining Substrate Specificities for Lipase and Phospholipase Candidates
Published on: November 23, 2016
Two-step activity-based protein profiling of diacylglycerol lipase
Eva J van Rooden1, Roy Kreekel, Thomas Hansen
1Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands. m.van.der.stelt@chem.leidenuniv.nl.
Abstract:
Diacylglycerol lipases (DAGL) produce the endocannabinoid 2-arachidonoylglycerol, a key modulator of neurotransmitter release. Chemical tools that visualize endogenous DAGL activity are desired. Here, we report the design, synthesis and application of a triazole urea probe for DAGL equipped with a norbornene as a biorthogonal handle. The activity and selectivity of the probe was assessed with activity-based protein profiling. This probe was potent against endogenous DAGLα (IC50 = 5 nM) and it was successfully applied as a two-step activity-based probe for labeling of DAGLα using an inverse electron-demand Diels-Alder ligation in living cells.
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