Interfacial and/or molecular recognition by lipases of mixed monomolecular films of 1,2-dicaprin and chiral organophosphorus glyceride analogues?

Enantiomerically pure sn-1,2- and sn-2,3-O-didecanoylphosphonoglycerides, were synthesised and investigated as inhibitors of human pancreatic lipase (HPL) and human gastric lipase (HGL). The inhibition studies were performed using the monomolecular film technique coupled with ELISA tests. All the four stereoisomers investigated reduced the hydrolysis of 1,2-dicaprin by both lipases. With HPL, they exhibited a rather weak inhibitory power and no significant differences were observed among them. With HGL, the inhibition depended much more strongly on the chirality at the sn-2 carbon of the glycerol backbone, while the chirality at the phosphorus had no influence. Moreover, a clear correlation was observed between the HGL surface concentration and the inhibitor surface molar fraction (α₅₀) leading to half inhibition. The greatest enzymatic inhibition was observed with films containing the enantiomeric inhibitor to which the HGL was best adsorbed, assuming thus that the interfacial lipase binding was controlled by a supramolecular chiral recognition process.