Glover C J, Tellez M R, Guziec F S, Felsted R L
Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Biochem Pharmacol. 1991;41(6-7):1067-74. doi: 10.1016/0006-2952(91)90215-q.
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 microM, the acyl CoA analog, S-(2-ketopentadecyl)-CoA, completely inhibited NMT in the presence of 80 microM 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 microM 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 microM. Two additional acyl CoA analogs, S-(cis-3-tetradecenoyl)-CoA and S-(3-tetradecynoyl)-CoA, functioned as alternative substrates for NMT.
合成了几种底物和产物类似物，并将其作为牛脑N-肉豆蔻酰辅酶A：蛋白质N-肉豆蔻酰转移酶（NMT；EC 2.3.1.97）的体外抑制剂进行测试。在40μM时，酰基辅酶A类似物S-(2-氧代十五烷基)-辅酶A在80μM肉豆蔻酰辅酶A存在下完全抑制NMT。在40μM肉豆蔻酰辅酶A存在下，酰基辅酶A类似物S-(2-溴十四烷酰)-辅酶A、S-(3-(环氧亚甲基)十二烷酰)-辅酶A以及多底物衍生物N-(2-S-辅酶A-十四烷酰)甘氨酰胺也观察到抑制作用减弱但明显。非辅酶A肉豆蔻酰类似物1-溴-2-十五烷酮也观察到抑制作用。上述所有化合物对肉豆蔻酰辅酶A均表现出可逆的竞争性抑制动力学，Ki值为0.11至24μM。另外两种酰基辅酶A类似物S-(顺式-3-十四碳烯酰)-辅酶A和S-(3-十四碳炔酰)-辅酶A作为NMT的替代底物发挥作用。
