Abstract
Based on the hypothesis that the bulky selenium atom, with 4p orbitals, can sterically hinder the approach of a cellular kinase to 5'-OH for phosphorylation, 4'-selenonucleosides with one-carbon homologation were designed and synthesized via a novel seleno-Michael reaction, with the stereoselectivity controlled by steric effects. 5'-Homo-4'-selenonucleosides (n = 2) demonstrated potent antiherpes simplex virus (HSV-1) activity, indicating that the bulky selenium atom might play a key role in preventing phosphorylation by cellular kinases, resulting in no antiviral activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Dideoxynucleosides / chemical synthesis*
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Dideoxynucleosides / chemistry
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Dideoxynucleosides / pharmacology*
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Herpesvirus 1, Human / chemistry*
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Herpesvirus 1, Human / drug effects
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Molecular Structure
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Nucleic Acid Conformation
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Organoselenium Compounds / chemical synthesis*
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Organoselenium Compounds / chemistry
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Organoselenium Compounds / pharmacology*
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Phosphorylation
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Simplexvirus / drug effects*
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Stereoisomerism
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Thymidine Kinase / chemistry*
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Thymidine Kinase / pharmacology*
Substances
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Antiviral Agents
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Dideoxynucleosides
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Organoselenium Compounds
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Thymidine Kinase