Abstract
Carbocyclic alpha, gamma-bis(nucleoside)-5,5'-triphosphonates and alpha, delta-bis(nucleoside)-5,5'-tetraphosphonates (Ap4A and Gp4G) analogues were shown to be a new type of terminating substrate of HIV reverse transcriptase. They effectively inhibited the DNA synthesis catalyzed by this enzyme in model cell-free systems, but their antiviral activity both in Rat1 fibroblast cell culture bearing MLV reverse transcriptase and in HIV-infected MT-4 cells was low. When a liposome delivery system was used, the antiviral efficacy of the compounds under study was increased.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / pharmacology
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Cells, Cultured
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Cyclopentanes / chemical synthesis
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Cyclopentanes / pharmacology
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HIV Reverse Transcriptase / antagonists & inhibitors*
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Humans
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Liposomes
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Nucleosides / chemical synthesis*
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Nucleosides / pharmacology
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Organophosphorus Compounds / chemical synthesis*
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Organophosphorus Compounds / pharmacology
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Rats
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
Substances
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Anti-HIV Agents
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Cyclopentanes
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Liposomes
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Nucleosides
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Organophosphorus Compounds
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Reverse Transcriptase Inhibitors
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polyphosphonate
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HIV Reverse Transcriptase