Conformationally constrained analogues of diacylglycerol having a perhydrofuro[3,4-c]furan-1,4-dione bis-gamma-butyrolactone skeleton.
Bis-gamma-lactones (1, 2) having a perhydrofuro[3,4-c]furan-1,4-dione skeleton were designed as conformationally constrained diacylglycerol analogues. They were synthesized from D-apiose in 11 steps, and evaluated as PKC-alpha ligands by measuring their ability to displace bound [3H]-PDBU from the enzyme. The compounds showed moderate binding affinities with Ki values of 13.89 (+/- 5.67) microM and 11.47 (+/- 0.89) microM, respectively. Their similar binding affinities indicate that these two bicyclic compounds were not effectively discriminated by PKC-alpha in terms of the direction of the side chain as other ligands built on similar bis-gamma-lactones.
Lee
J
J
College of Pharmacy, Seoul National University, Korea.
Lewin
N E
NE
Blumberg
P M
PM
Marquez
V E
VE
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005990:Glycerol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008024:Ligands; D015240:Phorbol 12,13-Dibutyrate / Q000493:pharmacokinetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008024:Ligands; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D005990:Glycerol