Synthesis of myristoyl-carba(dethia)-coenzyme A and S-(3-oxohexadecyl)-coenzyme A, two potent inhibitors of myristoyl-CoA:protein N-myristoyltransferase.
1. Two non-hydrolysable analogues of myristoyl-coenzyme A were synthesised and spectroscopically characterized. Myristoyl-carba(dethia)coenzyme A was prepared in a multistep synthesis starting from tridecyl vinyl ketone. S-(3-Oxohexadecyl)-coenzyme A was synthesised from 3-oxohexadecyl chloride by direct condensation with coenzyme A. 2. Both analogues were strong competitive inhibitors of N-myristoyltransferase from yeast. Ki values of 0.3 and 0.25 microM were determined for myristoyl-carba(dethia)-coenzyme A and S-(3-oxohexadecyl)-coenzyme A, respectively.
Wagner
A P
AP
Department of Biochemistry, University of Karlsruhe, Federal Republic of Germany.
Rétey
J
J
D000214:Acyl Coenzyme A / Q000138:chemical synthesis* / Q000494:pharmacology; D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D003065:Coenzyme A / Q000138:chemical synthesis / Q000494:pharmacology; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D000214:Acyl Coenzyme A; D007202:Indicators and Reagents; C067607:S-(3-oxohexadecyl)-coenzyme A; C067606:myristoyl-carba(dethia)-coenzyme A; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; D003065:Coenzyme A