The inhibitory mechanism of bovine pancreatic phospholipase A(2) by aldehyde terpenoids

We established the stereoselective synthesis of (E)-3-methoxycarbonyl-2,4,6 -trienal compound A and discovered that the compound A showed more powerful inhibitory activity toward phospholipase A(2)(PLA(2)) from bovine pancreas than manoalide which is a typical PLA(2) inhibitor. As the inhibitory mech anism of PLA(2) by A, the irreversible formation of dihydropyridine derivat ive resulting from the reaction of A with lysine residues in PLA(2) was pro posed based on the model reactions. Furthermore, A was found to selectively modify Lys56 which is included in the interfacial recognition site of this enzyme by the MALDI-TOF-MS peptide mapping analyses. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.