Conformationally constrained analogues of diacylglycerol. 18. The incorporation of a hydroxamate moiety into diacylglycerol-lactones reduces lipophilicity and helps discriminate between sn-1 and sn-2 binding modes to proteinkinase c (PK-C). Implications for isozyme specificity

An approach to reduce the log P in a series of diacylglycerol (DAG)-lactone s known for their high binding affinity for protein kinase C (PK-C) is pres ented. Branched alkyl groups with reduced lipophilicity were selected and c ombined with the replacement of the ester or lactone oxygens by NH or NOH g roups. Compound 6a with an isosteric N-hydroxyl amide arm represents the mo st potent and least lipophilic DAG analogue known to date.