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Analysis of Interactions of DNA polymerase β and reverse transcriptases of human immunodeficiency and mouse leukemia viruses with dNTP analogs containing a modified sugar residue

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Abstract

Substrate properties of various morpholinonucleoside triphosphates in the reaction of DNA elongation catalyzed by DNA polymerase β, reverse transcriptase of human immunodeficiency virus (HIV-1 RT), and reverse transcriptase of Moloney murine leukemia virus (M-MuLV RT) were compared. Morpholinonucleoside triphosphates were utilized by DNA polymerase β and HIV-1 reverse transcriptase as substrates, which terminated further synthesis of DNA, but were virtually not utilized by M-MuLV reverse transcriptase. The kinetic parameters of morpholinoderivatives of cytosine (MorC) and uridine (MorU) were determined in the reaction of primer elongation catalyzed by DNA polymerase β and HIV-1 reverse transcriptase. MorC was a more effective substrate of HIV-1 reverse transcriptase and significantly less effective substrate of DNA polymerase β than MorU. The possible use of morpholinonucleoside triphosphates as selective inhibitors of HIV-1 reverse transcriptase is discussed.

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Correspondence to O. I. Lavrik.

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Translated from Biokhimiya, Vol. 70, No. 1, 2005, pp. 5–13. Original Russian Text Copyright © 2005 by Lebedeva, Seredina, Silnikov, Abramova, Levina, Khodyreva, Rechkunova, Lavrik.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM04-241, December 5, 2004.

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Lebedeva, N.A., Seredina, T.A., Silnikov, V.N. et al. Analysis of Interactions of DNA polymerase β and reverse transcriptases of human immunodeficiency and mouse leukemia viruses with dNTP analogs containing a modified sugar residue. Biochemistry (Moscow) 70, 1–7 (2005). https://doi.org/10.1007/PL00021748

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  • DOI: https://doi.org/10.1007/PL00021748

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