Alkyl analogs of diacylglycerol as activators of protein kinase C.

Diacylglycerols which activate protein kinase C have the 1,2-sn configuration. Short-chain saturated fatty acids or long-chain unsaturated fatty acids are required for supporting the potency of these lipids. Using alkyl analogs such as 1-O-decyl-2-O-decanoylglycerol, 1-O-decanoyl-2-O-decylglycerol, 1,2-O-didecylglycerol, 1-O-hexadecyl-2-O-acetylglycerol and 1-O-decyl-2-O-acetylglycerol, we showed that the ether bond was consistently associated with a loss of activity to varying extents. The results suggest that the ester bond in the 1-position is a major determinant of diacylglycerol-mediated protein kinase activation.