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....

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Molecular biology (New York) 2014-09, Vol.48 (5), p.727-733
Hauptverfasser: Kukhanova, M. K., Korovina, A. N., Sharkin, Yu. A., Azhayev, A. V., Kochetkov, S. N.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
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.
ISSN:0026-8933
1608-3245
DOI:10.1134/S0026893314050082