Inhibition of HIV-1 reverse transcriptase by 5′-triphosphates of 5-substituted uridine analogs

The 5′-triphosphates of some 5-substituted 2′-deoxyuridine analogs were investigated for their effects on purified recombinant reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) as well as cellular DNA polymerase α. The triphosphates were competitive inhibitors of the viral enzyme with dTTP as the variable substrate and poly(rA)oligo(dT) as template, and preferentially inhibited the viral polymerase. Ordering the compounds according to their decreasing binding affinities, as reflected by their increasing inhibition constants for the reverse transcriptase, gave nPrearaUTP > nPrdUTP > EtdUTP > nPredUTP > HMdUTP > CEdUTP.