Iodoaryl analogues of dioctanoylglycerol and 1-oleoyl-2-acetylglycerol as probes for protein kinase C.
Analogues of dioctanoylglycerol (diC8) and 1-oleoyl-2-acetylglycerol (OAG) containing an iodoaryl group have been synthesized and shown to compete with [3H]phorbol dibutyrate [( ([3H]PDBu) for binding to protein kinase C in a crude rat brain preparation. Phorbol diesters have been shown to bind specifically to protein kinase C and the PDBu receptor has been copurified with protein kinase C activity. All three diacylglycerol analogues were comparable to OAG in binding affinity. In an assay of protein kinase C activation, the diC8 analogue was more active than the OAG analogues, thus demonstrating greater structural specificity under the conditions of this assay.
Department of Medicinal Chemistry, University of Michigan, Ann Arbor 48109-0626.
L M
LM
Strawn
R E
RE
Martell
R U
RU
Simpson
K L
KL
Leach
R E
RE
Counsell
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004075:Diglycerides / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000138:chemical synthesis* / Q000378:metabolism*; D006847:Hydrocarbons, Iodinated / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D015335:Molecular Probes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D004075:Diglycerides; D005989:Glycerides; D006847:Hydrocarbons, Iodinated; D015335:Molecular Probes; D015240:Phorbol 12,13-Dibutyrate; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C