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.
Strawn
L M
LM
Department of Medicinal Chemistry, University of Michigan, Ann Arbor 48109-0626.
Martell
R E
RE
Simpson
R U
RU
Leach
K L
KL
Counsell
R E
RE
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