The Mechanism of Interaction of Human Mitochondrial DNA Polymerase γ with the Novel Nucleoside Reverse Transcriptase Inhibitor 4' -Ethynyl-2-Fluoro-2' -Deoxyadenosine Indicates a Low Potential for Host Toxicity.


The potent 4' -ethynyl-2-fluoro-2' -deoxyadenosine (EFdA) is a ...
The potent 4' -ethynyl-2-fluoro-2' -deoxyadenosine (EFdA) is a promising experimental agent for treating HIV infection. Pre-steady-state kinetics were used to characterize the interaction of EFdA-triphosphate (EFdA-TP) with human mitochondrial DNA polymerase γ (Pol γ) to assess the potential for toxicity. Pol γ incorporated EFdA-TP 4,300-fold less efficiently than dATP, with an excision rate similar to ddATP. This strongly indicates EFdA is a poor Pol γ substrate suggesting minimal Pol γ-mediated toxicity, although this should be examined under clinical settings.




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