Abstract
A nucleoside analogue 4'-ethynylstavudine (4'-Ed4T) was recently synthesized during chemical studies directed towards the development of a new route to 4'-carbon-substituted nucleosides. This compound was found to be more anti-HIV-1 active than the parent compound stavudine (d4T) and much less toxic to various cells and also to mitochondrial DNA synthesis. It became apparent that 4'-Ed4T is a better substrate for human thymidine kinase than d4T, and very much more resistant to catabolism by thymidine phosphorylase. The study of 4'-Ed4T against various drug-resistant HIV-1 mutants has disclosed its unique activity profile.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology*
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Cell Line
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DNA, Mitochondrial / drug effects
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DNA, Mitochondrial / metabolism
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Drug Resistance, Viral / genetics
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HIV-1 / drug effects*
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HIV-1 / genetics
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Humans
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Molecular Structure
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Mutation
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Stavudine / analogs & derivatives*
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Stavudine / chemistry
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Stavudine / pharmacology
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Structure-Activity Relationship
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Substrate Specificity
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Thymidine Kinase / metabolism
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Thymidine Phosphorylase / metabolism
Substances
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4'-ethynylstavudine
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Anti-HIV Agents
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DNA, Mitochondrial
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Stavudine
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Thymidine Phosphorylase
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Thymidine Kinase