The 5′-triphosphates of 3′-azido-3′-deoxythymidine and 2′, 3′-dideoxynucleosides inhibit DNA polymerase γ by different mechanisms

Inhibition mechanisms of 5′-triphosphates of 3′-azido-3′-deoxythymidine (AZT-TP) and 3′-deoxythymidine (ddTTP) on extensively purified DNA polymerase γ from bovine testes were examined by analysis of the products synthesized on singly primed M13 single-stranded DNA or synthetic oligonucleotide template-primer in the presence of analogues. The results indicate that AZT-TP inhibits DNA polymerase γ in competition with dTTP but is not incorporated into DNA, whereas ddTTP is incorporated into DNA and causes chain termination. In contrast, both analogues were used by reverse transcriptase and caused chain termination.