Inhibition of mandelate racemase by the substrate–intermediate–product analogue 1,1-diphenyl-1-hydroxymethylphosphonate

Mandelate racemase has been studied as a paradigm for enzyme-catalyzed abstraction of a proton from carbon acids with relatively high pKa values. 1,1-Diphenyl-1-hydroxymethylphosphonate is a substrate–intermediate–product analogue and is a modest competitive inhibitor of the enzyme (Ki = 1.41 ± 0.09 mM), suggesting that simultaneous binding of the two phenyl groups obviates mimicry of the aci-carboxylate function of the intermediate by the phosphonate group.