Chiral discrimination of enantiomeric 2'-deoxythymidine 5'-triphosphate by HIV-1 reverse transcriptase and eukaryotic DNA polymerases

Biochemical and Biophysical Research Communications
T YamaguchiM Saneyoshi

Abstract

Inhibitory effects of 2'-deoxy-L-thymidine 5'-triphosphate (L-dTTP), the enantiomer of the natural substrate D-dTTP, on the activity of mammalian DNA polymerases alpha, beta and gamma, Escherichia coli DNA polymerase I and human immunodeficiency virus 1 (HIV-1) reverse transcriptase were examined. When poly(rA)n-oligo(dT)12-18 was used as the template-primer, L-dTTP showed remarkable inhibitory effect on HIV-1 reverse transcriptase in competitive fashion with respect to the substrate dTTP. In contrast, L-dTTP did not inhibit DNA polymerases alpha and was slightly inhibitory to DNA polymerase beta. These results suggest that the nuclear DNA polymerases alpha and beta showed high specificity for the substrate with the natural configuration of the sugar moiety, D-dTTP, exhibiting little or no ability to recognize L-dTTP, whereas HIV-1 reverse transcriptase essentially lacked the ability to differentiate the D- and L-sugar moieties.

Citations

Oct 1, 1996·Journal of Biomolecular Structure & Dynamics·A A Krayevsky, D N Chernov
Jul 5, 2005·Expert Opinion on Investigational Drugs·S SpadariF Focher
Feb 20, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Valeria Famiglini, Romano Silvestri
Sep 21, 2001·Nucleosides, Nucleotides & Nucleic Acids·T YamaguchiM Saneyoshi
Dec 16, 2003·Biochemical and Biophysical Research Communications·Hidehito UrataMasao Akagi

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