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

K Nacro; B Bienfait; N E Lewin; P M Blumberg; V E Marquez

doi:10.1016/s0960-894x(00)00070-6

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

Bioorg Med Chem Lett. 2000 Apr 3;10(7):653-5. doi: 10.1016/s0960-894x(00)00070-6.

Authors

K Nacro¹, B Bienfait, N E Lewin, P M Blumberg, V E Marquez

Affiliation

¹ Laboratories of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

PMID: 10762046
DOI: 10.1016/s0960-894x(00)00070-6

Abstract

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.

MeSH terms

Diglycerides / chemical synthesis
Diglycerides / chemistry
Diglycerides / pharmacology*
Enzyme Activators / chemical synthesis
Enzyme Activators / chemistry
Enzyme Activators / pharmacology*
Glycerol / chemistry
Lactones / chemical synthesis
Lactones / chemistry
Lactones / pharmacology*
Ligands
Protein Kinase C / drug effects
Protein Kinase C / metabolism*
Structure-Activity Relationship

Substances

Diglycerides
Enzyme Activators
Lactones
Ligands
Protein Kinase C
Glycerol