Add time:07/30/2019         Source:sciencedirect.com

Several substrate and product analogs were synthesized and tested as in vitro inhibitors of bovine brain N-myristoyl-CoA:protein N-myristoyltransferase (NMT; EC 2.3.1.97). At 40 μM, the acyl CoA analog, S-(2-ketopentadecyl)-CoA, completely inhibited NMT in the presence of 80 μM myristoyl CoA. Decreasing but marked inhibition was also observed with the acyl CoA analogs, S-(2-bromo-tetradecanoyl)-CoA and S-(3-(epoxymethylene)dodecanoyl)-CoA, and the multisubstrate derivative N-(2-S-CoA-tetradecanoyl)glycinamide in the presence of 40 μm myristoyl CoA. Inhibition was also observed with the non-coenzyme A myristoyl analog, 1-bromo-2-pentadecanone. All of the above compounds exhibited reversible competitive inhibition kinetics with respect to myristoyl CoA with Ki, values of 0.11 to 24 μM. Two additional acyl CoA analogs, S-(cis-3-tetradecenoyl)-CoA and S-(3-tetradecynoyl)-CoA, functioned as alternative substrates for NMT.

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