Covalent inhibition of digestive lipases by chiral phosphonates

Designing and synthesizing specific inhibitors is of fundamental value for understanding the molecular mechanisms involved in the interfacial adsorpti on step as well as the catalytic activity of lipases. In this Account, we w ill review and discuss results obtained mostly at our laboratory concerning the covalent inhibition of human gastric and human pancreatic lipases by c hiral phosphonates. Rather than presenting an exhaustive list of compounds tested so far with lipases of animal and microbial origin, we selected rece nt experimental data illustrating well the specific problems encountered du ring the covalent inhibition of these digestive lipases.