Endocannabinoids play an essential role in human health and disease, regulating processes such as immunomodulation, energy balance and neurotransmission. Diacylglycerollipase-α (DAGL-α) is responsible for the production of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the central nervous system. It is a potential drug target for the treatment of obesity and neurodegenerative diseases. Currently, there are no selective inhibitors and activity-based probes available for its study. The identification of selective DAGL- inhibitors is hampered by a lack of assays that make use of endogenous DAGL- activity in proteomes. Determination of the selectivity of the inhibitors in native tissues is important, because DAGL- belongs to the class of serine hydrolases, containing more than 200 members with various physiological functions. Here, I will present a chemical biology approach to identify and characterize highly selective chemical probes to study the function of this protein both in vitro and in vivo.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech
