CONFORMATIONALLY CONSTRAINED ANALOGS OF DIACYLGLYCEROL (DAG) .4. INTERACTION OF ALPHA-ALKYLIDENE-GAMMA-LACTONES WITH PROTEIN-KINASE-C (PK-C)

Isomeric alpha-alkylidene-gamma-lactones with a C-14 chain were synthe sized and evaluated as inhibitors of phorbol ester binding to protein kinase C (PK-C). While the Z-isomer 3 was the most potent inhibitor (K (i) = 0.2 muM), the stereochemistry at the alpha-position of the lacto ne appears to have only a modest effect in modulating PK-C binding. Th e same appears to be true for both isomeric alpha-alkyl-gamma-lactones which were obtained by catalytic hydrogenation of the unsaturated lac tones.