Tenofovir Diphosphate Is a Poor Substrate and a Weak Inhibitor of Rat DNA Polymerases α, δ, and ε*

Abstract

Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol) α, δ, and ε*, with values for the K_i for PMPApp (^PMPAppK_i) relative to the K_m for dATP (^dATPK_m) of 10.2, 10.2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with ^PMPAppK_m values 350-, 2,155-, and 187-fold higher than ^dATPK_m values for pol α, δ, and ε*, respectively.