Activity-based protein profiling of diacylglycerol lipases

Baggelaar, M.P. (2017)

Doctoral Thesis

Diacylglycerol lipase (DAGL)-α and -β are enzymes responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. Selective and reversible inhibitors are required to study the function of DAGLs in neuronal cells in an acute and temporal fashion. The work described in this thesis has led to the identification of an activity-based probe (ABP) for DAGL-α. This ABP was instrumental for the identification of a new class of highly selective DAGL inhibitors. These novel inhibitors can be used to investigate the role of the diacylglycerol lipases in metabolic syndrome and neurodegenerative diseases such a Parkinson’s disease, Alzheimer’s disease and Multiple Sclerosis.

• Activity-based protein profiling
• 2-arachidonoylglycerol
• Proteomics
• Diacylglycerol lipase
• Inhibitor

• All authors: Baggelaar, M.P.
• Supervisor: Overkleeft, H.S.
• Co-supervisor: Stelt, M. van der
• Committee: Cravatt, B.F.; Ovaa, H.; Boeckel, C.A.A. van; Marel, G.A. van der; Brouwer, J.; Bonger, K.
• Qualification: Doctor (dr.)
• Awarding Institution: Molecular physiology, Science, Leiden University
• Date: 2017-04-06
• ISBN (print): 9789462995512