Conformationally constrained analogues of diacylglycerol (DAG). 14. Dissection of the roles of the sn-1 and sn-2 carbonyls in DAG mimetics by isopharmacophore replacement.
The replacement of the sn-1 and sn-2 carbonyl esters in DAG-surrogate lactones by sulfonate esters showed that their isosteric properties in protein kinase C binding are controlled by the location of the hydrophobic alkyl chain on the molecule. The CO and SO2 groups appear to be true isosteres only when they are adjacent to the alkyl chain, which is presumed to insert normal to the lipid bilayer.
Marquez
V E
VE
Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Sharma
R
R
Wang
S
S
Lewin
N E
NE
Blumberg
P M
PM
Kim
I S
IS
Lee
J
J
D004075:Diglycerides / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism
D004075:Diglycerides; D008051:Lipid Bilayers; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C