Alkyl-linked diglycerides inhibit protein kinase C activation by diacylglycerols.
Alkylacylglycerols are synthesized when choline-phospholipids are degraded by a phospholipase C. This class of compounds has been shown to have biological activities; however, the mechanism of action is unknown. A series of alkyl-linked diglycerides were synthesized and tested for activity in an in vitro assay for protein kinase C. When protein kinase C activity was stimulated with the synthetic diacylglyceride analog 1-oleoyl-2-acetyl-sn-glycerol, the addition of alkyl glycerides caused a concentration-dependent inhibition of protein kinase C activity. Comparison of the protein kinase C inhibition by this series of 1-O-alkyl-2-acyl analogs revealed that both saturated and unsaturated long-chain groups in position 1 were effective and that dietherglycerols with short-chain moieties in position 2 were also effective. It is concluded from these studies that the biological activity of alkyl-linked glycerides may be expressed through protein kinase C inhibition.
Daniel
L W
LW
Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103.
Small
G W
GW
Schmitt
J D
JD
Marasco
C J
CJ
Ishaq
K
K
Piantadosi
C
C
D002460:Cell Line; D004075:Diglycerides / Q000138:chemical synthesis / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology*; D005995:Glyceryl Ethers / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D004075:Diglycerides; D005989:Glycerides; D005995:Glyceryl Ethers; C038237:1-oleoyl-2-acetylglycerol; C055394:1-palmityl-2-acetylglycerol; D011493:Protein Kinase C