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

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

In: Nucleic Acids Research, 1998, vol. 26, no. 17, p. 4063-4067

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    Titre
    • 4′-Acylated thymidine 5′-triphosphates: a tool to increase selectivity towards HIV-1 reverse transcriptase
    Auteur
    • Marx, Andreas. Department of Chemistry, University of Basel, St Johanns-Ring 19, CH-4056 Basel, Switzerland, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, Klingelbergstrasse 70, CH-4056 Basel, Switzerland
    • Giese, Bernd. Department of Chemistry, University of Basel, St Johanns-Ring 19, CH-4056 Basel, Switzerland, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, Klingelbergstrasse 70, CH-4056 Basel, Switzerland
    • Amacker, Mario. Department of Veterinary Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    • Stucki, Manuel. Department of Veterinary Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    • Hübscher, Ulrich. Department of Veterinary Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    • Bickle, Thomas A.. Division of Molecular Microbiology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Nucleic Acids Research, 1998, vol. 26, no. 17, p. 4063-4067. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:298149
    Summary
    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