TETROXOPRIM - NEW INHIBITOR OF BACTERIAL DIHYDROFOLATE-REDUCTASE

Dihydrofolate-reductase of E. coli MRE 600 was concentrated 16-fold by ion-exchange chromatography. The Michaelis constant (km) obtained for dihydrofolate was 2 7 x 10-5M. The inhibition constant (Ki) obtained for tetroxoprim were 3 2 x 10-9M and 4 0 x 10-9M for trimethoprim, respectively. The Michaelis con-stant of commercial dihydrofolate-reductase from bovine liver, determined for the substrate dihydrofolate was l 2xl0-4m and was independent of additional inhibitors in low concentrations. It was shown that the concentrations of tetroxoprim and trimethoprim which cause a 50% inhibition of the mammalian enzyme, are at least 60,000 and 50,000 fold higher than those which cause appropriate inhibition of the bacterial enzyme. © 1979 Oxford University Press.