Abstract
Zintevir is an oligonucleotide analogue, which has the phosphorothioate modification at both termini, that forms a K(+)-induced quadruplex structure and shows potent anti-human immunodeficiency virus (HIV)-1 activity. We synthesized the non-modified analogue (D-17mer) of Zintevir and its enantiomer (L-17mer), and compared their anti-HIV-1 activity and molecular mechanism of action. Although L-17mer forms the exact mirror image quadruplex structure of D-17mer, which has a very similar structure with Zintevir, L-17mer showed comparable anti-HIV-1 activity with Zintevir. The results obtained by the time-of-addition experiments and the immunofluorescence binding assay strongly suggest that the primary molecular target of L-17mer is the viral gp120 envelope protein as well as Zintevir, regardless of their reciprocal chirality.
Publication types
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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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Antibodies, Monoclonal / metabolism
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Base Sequence
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CD4 Antigens / immunology
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Cell Line, Transformed
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Circular Dichroism
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Drug Stability
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Flow Cytometry
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Genes, gag / drug effects
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Genes, gag / genetics
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HIV Envelope Protein gp120 / immunology
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Humans
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Nucleic Acid Conformation
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Oligonucleotides / chemical synthesis
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Oligonucleotides / chemistry*
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Oligonucleotides / metabolism
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Oligonucleotides / pharmacology*
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Phosphodiesterase I / metabolism
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Single-Strand Specific DNA and RNA Endonucleases / metabolism
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Stereoisomerism
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Temperature
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Time Factors
Substances
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Anti-HIV Agents
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Antibodies, Monoclonal
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CD4 Antigens
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HIV Envelope Protein gp120
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Oligonucleotides
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T 30177
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Single-Strand Specific DNA and RNA Endonucleases
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Phosphodiesterase I
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phosphodiesterase I, snake venom