Synthesis and structure-activity relationship of liposomal substrates for phospholipase A(2)

Abstract

A recent innovation in the use of liposomes as drug delivery systems consists of covalently attaching an anticancer drug at the sn-2 position of phospholipids. However, some of those lipids could not be hydrolyzed by sPLA2. Steric bulk in the vicinity of the sn-2 position appears to prevent hydrolysis of the substrate. Structurally different lipids have been synthesized and formulated as liposomes, subjected to sPLA2 and the hydrolysis rates have been compared to Molecular Dynamics simulations of the enzyme/substrate complexes