Abstract
A series of novel N1 alkylated purine nucleic acids were polymerized either enzymatically or by automated synthesis to further establish the SAR requirements for HIV, RT, and HCMV activity. Out of the series, two constructs, 2'-O-methyl-1-allylinosinic acid phosphorothioate 33-mer (16) and an oligomer incorporating 1-propyl-6-thioinosinic acid residues (20), were found to be highly active under all three assay conditions. SAR studies indicate that sulfur incorporation, high molecular weight, and low steric bulk at N1 all can be important for activity.
MeSH terms
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Allyl Compounds / chemical synthesis
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Allyl Compounds / chemistry
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Allyl Compounds / pharmacology
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology
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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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Cell Survival
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Cytomegalovirus / drug effects
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HIV-1 / drug effects
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Humans
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Inosine Monophosphate / chemistry
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Oligoribonucleotides / chemical synthesis
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Oligoribonucleotides / chemistry
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Oligoribonucleotides / pharmacology
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Polymers
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Polynucleotides / chemical synthesis*
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Polynucleotides / chemistry
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Polynucleotides / pharmacology
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Reverse Transcriptase Inhibitors / chemical synthesis
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Reverse Transcriptase Inhibitors / chemistry
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
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Thionucleotides / chemical synthesis
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Thionucleotides / chemistry
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Thionucleotides / pharmacology
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Tumor Cells, Cultured
Substances
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Allyl Compounds
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Anti-HIV Agents
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Antiviral Agents
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Oligoribonucleotides
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Polymers
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Polynucleotides
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Reverse Transcriptase Inhibitors
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Thionucleotides
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Inosine Monophosphate