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4'-Acylated thymidine 5'-triphosphates : a tool to increase selectivity towards HIV-1 reverse transcriptase

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1998

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Giese, Bernd
Amacker, Mario
Stucki, Manuel
Hübscher, Ulrich
Bickle, Thomas A.

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Nucleic Acids Research. 1998, 26(17), pp. 4063-4067. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/26.17.4063

Zusammenfassung

4′-Acylated thymidines represent a new class of DNA chain terminators, since they have been shown to act as post-incorporation chain-terminating nucleotides despite the presence of a free 3′-hydroxyl group. Here, we describe the action of the 4′-acetyl- (MeTTP) and 4′-propanoylthymidine 5′-triphosphate (EtTTP) on HIV-1 reverse transcriptase in RNA- and DNA-dependent DNA synthesis and on DNA synthesis catalyzed by the cellular DNA polymerases α, β, δ and ε. MeTTP exhibits a high selectivity towards HIV-1 reverse transcriptase. By the use of the bulkier propanoyl group as the 4′-substituent of the nucleoside 5′-triphosphate, selectivity towards HIV-1 reverse transcriptase could be increased without affecting substrate efficiency. Thus, 4′-modifications may serve as a tool to increase selectivity towards HIV-1 reverse transcriptase.

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540 Chemie

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ISO 690MARX, Andreas, Bernd GIESE, Mario AMACKER, Manuel STUCKI, Ulrich HÜBSCHER, Thomas A. BICKLE, 1998. 4'-Acylated thymidine 5'-triphosphates : a tool to increase selectivity towards HIV-1 reverse transcriptase. In: Nucleic Acids Research. 1998, 26(17), pp. 4063-4067. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/26.17.4063
BibTex
@article{Marx1998-09-014Acyl-33965,
  year={1998},
  doi={10.1093/nar/26.17.4063},
  title={4'-Acylated thymidine 5'-triphosphates : a tool to increase selectivity towards HIV-1 reverse transcriptase},
  number={17},
  volume={26},
  issn={0305-1048},
  journal={Nucleic Acids Research},
  pages={4063--4067},
  author={Marx, Andreas and Giese, Bernd and Amacker, Mario and Stucki, Manuel and Hübscher, Ulrich and Bickle, Thomas A.}
}
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