Peptide conformational disorder in molecular recognition and inhibition of lipases

Lipases are essential enzymes in fat metabolism. Gastrointestinal lipases such as gastric and pancreatic lipases are involved in the digestion of dietary triglycerides and the intestinal absorption of their lipolysis products, free fatty acids and monoglycerides. Reducing fat absorption by inhibiting gastrointestinal lipases is a successful pharmacological approach in the treatment of obesity and the lipase inhibitor Orlistat (the active principle in Xenical and Alli) is today the first anti-obesity drug on the market. So far, lipase inhibitors are missing specificity within the lipase family and there is therefore a need for developing more specific lipase inhibitors. Our goal is to synthesize new lipase inhibitors based on intrinsically disordered peptides (IDPs) endowed with specificity.