TY - JOUR
T1 - Two-step activity-based protein profiling of diacylglycerol lipase
AU - Van Rooden, Eva J.
AU - Kreekel, Roy
AU - Hansen, Thomas
AU - Janssen, Antonius P.A.
AU - Van Esbroeck, Annelot C.M.
AU - Den Dulk, Hans
AU - Van Den Berg, Richard J.B.H.N.
AU - Codée, Jeroen D.C.
AU - Van Der Stelt, Mario
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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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U2 - 10.1039/c8ob01499j
DO - 10.1039/c8ob01499j
M3 - Article
C2 - 30004552
AN - SCOPUS:85050653562
SN - 1477-0520
VL - 16
SP - 5250
EP - 5253
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 29
ER -