2′-Fluoronucleotides as substrates of viral replicative polymerases
Substrate specificities of three viral replicative polymerases of different origins (HIV reverse transcriptase, hepatitis C virus RNA polymerase, and herpes virus DNA polymerase) towards 2′F-NTP were studied. Activated DNA, polyA-oligoU 6 , and (2′F-A) 20 -oligoU 6 complexes were used as templates....
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Veröffentlicht in: | Molecular biology (New York) 2014-09, Vol.48 (5), p.727-733 |
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Sprache: | eng |
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Zusammenfassung: | Substrate specificities of three viral replicative polymerases of different origins (HIV reverse transcriptase, hepatitis C virus RNA polymerase, and herpes virus DNA polymerase) towards 2′F-NTP were studied. Activated DNA, polyA-oligoU
6
, and (2′F-A)
20
-oligoU
6
complexes were used as templates. It was shown that all DNA polymerases studied incorporate 2′F-NMP into the 3′-end of primer-template complexes. HIV reverse transcriptase and herpes virus DNA polymerase can elongate synthesis with both dNTP and 2′F-NTP. Homopolymer (2′F-A)
20
can serve as a template for the polymerization of UTP as well as 2′F-UTP catalyzed by hepatitis C virus polymerase although with the efficacy about five-to tenfold lower compared to the natural primer-template complex. The pyrophosphorolysis reaction of 2′F-CMP residue on the 3′-end of the primer catalyzed with HIV reverse transcriptase proceeds with an efficiency that is two orders of magnitude less compared to the natural dNMP residues in the same system. |
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ISSN: | 0026-8933 1608-3245 |
DOI: | 10.1134/S0026893314050082 |