Abstract
DNA triplexes with hydrophobic modifications were designed and evaluated for their activity as inhibitors of the cell fusion of human immunodeficiency virus type 1 (HIV-1). Triplex inhibitors displayed low micromolar activities in the cell-cell fusion assay and nanomolar activities in the anti-HIV-1 pseudovirus test. Helix structure and the presence of sufficient numbers of hydrophobic regions were essential for the antifusion activity. Results from native polyacrylamide gel electrophoresis and a fluorescent resonance energy transfer-based inhibitory assay indicated that these triplexes may interact with the primary pocket at the glycoprotein 41 (gp41) N-heptad repeat, thereby inhibiting formation of the HIV-1 gp41 6-helical bundle. Triplex-based complexes may represent a novel category of HIV-1 inhibitors in anti-HIV-1 drug discovery.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Biological Assay
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Cell Fusion
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Cell Line, Transformed
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DNA / chemical synthesis
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DNA / chemistry
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DNA / pharmacology*
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Electrophoresis, Polyacrylamide Gel
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Fluorescence Resonance Energy Transfer
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HIV Envelope Protein gp41 / antagonists & inhibitors*
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HIV Envelope Protein gp41 / chemistry
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HIV Envelope Protein gp41 / metabolism
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HIV-1 / chemistry
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HIV-1 / drug effects*
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HIV-1 / metabolism
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HeLa Cells
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Humans
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Hydrophobic and Hydrophilic Interactions
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Models, Molecular
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Molecular Sequence Data
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Nucleic Acid Conformation
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Oligodeoxyribonucleotides / chemical synthesis
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Oligodeoxyribonucleotides / chemistry
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Oligodeoxyribonucleotides / pharmacology*
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Protein Binding / drug effects
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Protein Conformation
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Virus Internalization / drug effects*
Substances
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HIV Envelope Protein gp41
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Oligodeoxyribonucleotides
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triplex DNA
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DNA