Evidence that a second stereochemical centre in diacylglycerols defines interaction at the recognition site on protein kinase C.
The interaction of novel diacylglycerol analogues at the recognition site on protein kinase C has been evaluated using a modified [3H]phorbol dibutyrate binding assay and an established kinase activation assay. Studies with the 3-methyl analogues of 1,2-dihexanoyl-sn-glycerol have revealed a preferred stereochemical configuration at the C-3 position. Other chemical modifications have extended existing structure/activity relationships by showing that carbamates and sulphonyl esters cannot substitute for carboxylate esters and that cyclic acyl groups are active. Thus, most, if not all of the functionalities in the diacylglycerol molecule are required for interaction at the receptor on protein kinase C. Stereochemical specificity is required at C2 and C3.
Bonser
R W
RW
Department of Biochemical Sciences, Wellcome Research Laboratories, Beckenham, England.
Thompson
N T
NT
Hodson
H F
HF
Beams
R M
RM
Garland
L G
LG
D001665:Binding Sites; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation; D005989:Glycerides / Q000494:pharmacology*; D007700:Kinetics; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004075:Diglycerides; D005989:Glycerides; D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C