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.