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• W2056598588 abstract "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. Although nPredUTP was less inhibitory than nPrearaUTP under conditions of competitive inhibition, nPredUTP caused a time- and concentration-dependent inactivation of reverse transcriptase activity when preincubated with template. This inactivation was not reversed by excess dTTP. The decrease in template-primer activity did not occur with nPrearaUTP, but was shown with the chain-terminating 5′-triphosphates of 3′-fluoro- and 3′-azidothymidine. As nPredUTP, but not nPrearaUTP, was an alternative substrate, shown by the ability to support DNA synthesis in absence of competing substrate, the incorporation of nPredUTP into the primer-template apparently leads to increased inhibition of the enzyme." @default.
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• W2056598588 date "1989-12-01" @default.
• W2056598588 modified "2023-09-25" @default.
• W2056598588 title "Inhibition of HIV-1 reverse transcriptase by 5′-triphosphates of 5-substituted uridine analogs" @default.
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• W2056598588 doi "https://doi.org/10.1016/0166-3542(89)90054-5" @default.
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