Synthetic branched-chain analogues of distearoylphosphatidyl-choline: Structure-activity relationship in inhibiting and activating protein kinase C

A series of distearoyl-phosphatidylcholine (DSPC) analogues having various branched alkyl chains were synthesized and tested for their abilities to regulate protein kinase C (PKC). The greatest improvement (about 3-fold) in the PKC inhibitory activity over that seen for the parental lipid (i.e., DSPC) was accomplished by substitution of 8-methylstearate at sn-2 and 16-methylstearate at both sn-1 and sn-2 positions of glycerol; substitutions at both sn-1 and sn-2 with 8-methylstearate, on the other hand, caused a decrease (about 4-fold) in its inhibitory activity. The findings suggest that DSPC analogues having different branched-chain fatty alkyl chains exhibited altered abilities to regulate PKC, probably reflecting in part some unique physicochemical properties of the analogues capable of critically modifying the activation process of the PKC system.