Development of an Activity-Based Probe and In Silico Design Reveal Highly Selective Inhibitors for Diacylglycerol Lipase-α in Brain

A model method: A strategy that combines a knowledge‐based in silico design approach and the development of novel activity‐based probes (ABPs) for the detection of endogenous diacylglycerol lipase‐α (DAGL‐α) is presented. This approach resulted in the rapid identification of new DAGL‐α inhibitors wi...

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Veröffentlicht in:	Angewandte Chemie International Edition 2013-11, Vol.52 (46), p.12081-12085
Hauptverfasser:	Baggelaar, Marc P., Janssen, Freek J., van Esbroeck, Annelot C. M., den Dulk, Hans, Allarà, Marco, Hoogendoorn, Sascha, McGuire, Ross, Florea, Bogdan I., Meeuwenoord, Nico, van den Elst, Hans, van der Marel, Gijsbert A., Brouwer, Jaap, Di Marzo, Vincenzo, Overkleeft, Herman S., van der Stelt, Mario
Format:	Artikel
Sprache:	eng
Schlagworte:	activity-based probe Animals Arachidonic Acids - metabolism Binding Sites Brain - enzymology Brain - metabolism Cell Membrane - metabolism drug discovery endocannabinoid Endocannabinoids - metabolism Enzyme Inhibitors - chemistry Enzyme Inhibitors - metabolism Glycerides - metabolism HEK293 Cells Humans hydrolases Lipoprotein Lipase - antagonists & inhibitors Lipoprotein Lipase - genetics Lipoprotein Lipase - metabolism Mice Protein Binding Protein Structure, Tertiary Proteome proteomics Structure-Activity Relationship
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Zusammenfassung:	A model method: A strategy that combines a knowledge‐based in silico design approach and the development of novel activity‐based probes (ABPs) for the detection of endogenous diacylglycerol lipase‐α (DAGL‐α) is presented. This approach resulted in the rapid identification of new DAGL‐α inhibitors with high selectivity in the brain proteome. ABPP=activity‐based protein profiling.
ISSN:	1433-7851 1521-3773
DOI:	10.1002/anie.201306295