Diacylglycerols with lipophilically equivalent branched acyl chains display high affinity for protein kinase C (PK-C). A direct measure of the effect of constraining the glycerol backbone in DAG lactones.
New synthetic diacylglycerols (DAGs) with equivalent branched acyl chains were compared with commercially available DAGs as PK-C ligands. The results support the view that there is a minimal lipophilic requirement provided by the equivalent acyl groups that results in high binding affinity. Locking the glycerol backbone of the most potent DAG into a five-member lactone resulted in a 10-fold increase in potency.
Nacro
K
K
Laboratories of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Bienfait
B
B
Lewin
N E
NE
Blumberg
P M
PM
Marquez
V E
VE
D004075:Diglycerides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020536:Enzyme Activators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005990:Glycerol / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004075:Diglycerides; D020536:Enzyme Activators; D007783:Lactones; D008024:Ligands; D011493:Protein Kinase C; D005990:Glycerol