CONFORMATIONALLY CONSTRAINED ANALOGS OF DIACYLGLYCEROL .9. THE EFFECTOF SIDE-CHAIN ORIENTATION ON THE PROTEIN-KINASE-C (PK-C) BINDING-AFFINITY OF DELTA-LACTONES

The construction of conformationally constrained diacylglycerol analog ues on an alpha-alkylidene-delta-lactone template was achieved stereos pecifically from L-xylose. The increased PK-C binding affinity of the E-isomer (6) over the Z-isomer (5) contrasts with the more modest diff erence observed for the same geometrical isomers built on an alpha-alk ylidene-gamma-lactone template. The more effective discrimination betw een isomeric alpha-alkylidene-delta-lactones by PK-C forcefully argues that orientation of the side-chain is a key determinant for a strong interaction with the enzyme.