Type I isopentenyl diphosphate isomerase is a metal-dependent enzyme that generates a tertiary carbocation intermediate during catalysis. This study describes an inhibitor (2-guanidinoethyl(dihydroxyphosphorylmethyl)phosphinate) of the isomerase that bears a guanidinium as a carbocation mimic and a phosphinylphosphonate as a non-hydrolyzable metal binding functionality. Inhibition kinetics show that the compound acts in a competitive manner with a K_i value of 129 nM (K_M,IPP/K_i = 27). An analogous inhibitor bearing a tertiary ammonium as the carbocation mimic was 50-fold less potent, suggesting that the planar guanidinium is a more effective carbocation mimic. Inhibitors bearing an acylated methanesulfonamide or a hydroxamate group in place of the pyrophosphate inhibited the enzyme at millimolar concentrations indicating that the isomerase is highly specific for binding to the diphosphate portion of the intermediate.

I 型异戊烯二磷酸异构酶是一种金属依赖性酶，在催化过程中产生叔碳正离子中间体。该研究描述了异构酶的抑制剂（2-胍基乙基（二羟基磷酰甲基）次膦酸盐），它带有胍盐作为碳阳离子模拟物和膦酰膦酸盐作为不可水解的金属结合功能。抑制动力学表明该化合物以竞争方式发挥作用，K _i值为 129 nM ( K _M,IPP / K _i = 27)。带有叔铵作为碳阳离子模拟物的类似抑制剂的效力要低 50 倍，这表明平面胍是一种更有效的碳阳离子模拟物。带有酰化甲磺酰胺或异羟肟酸酯基团代替焦磷酸盐的抑制剂在毫摩尔浓度下抑制酶，表明异构酶对结合中间体的二磷酸盐部分具有高度特异性。