Discovery of arginine-containing tripeptides as a new class of pancreatic lipase inhibitors

AIM: The inhibition of pancreatic lipase (PL) represents one of the most promising strategies in the search for novel antiobesity drugs. We propose here a pioneering course by exploring tripeptide scaffolds in the way to selective PL inhibitors. METHODOLOGY/RESULTS: The peptide series exhibited good PL inhibitory properties in vitro, with all the strongest inhibitors sharing a central arginine, shown in silico to be relevant for the active site-directed activity. The compounds were found devoid of inhibitory properties on acetylcholinesterase.