Abstract
Human immunodeficiency virus type-1 (HIV-1) membrane fusion is promoted by the formation of a trimer-of-hairpins structure that brings the amino- and carboxyl-terminal regions of the gp41 envelope glycoprotein ectodomain into close proximity. Peptides derived from the carboxyl-terminal region (called C-peptides) potently inhibit HIV-1 entry by binding to the gp41 amino-terminal region. To test the converse of this inhibitory strategy, we designed a small protein, denoted 5-Helix, that binds the C-peptide region of gp41. The 5-Helix protein displays potent (nanomolar) inhibitory activity against diverse HIV-1 variants and may serve as the basis for a new class of antiviral agents. The inhibitory activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing antibody response that targets the carboxyl-terminal region of the gp41 ectodomain.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Anti-HIV Agents* / chemistry
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Anti-HIV Agents* / immunology
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Anti-HIV Agents* / metabolism
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Anti-HIV Agents* / pharmacology
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism
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Carrier Proteins / pharmacology*
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Cell Line
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Drug Design*
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Giant Cells / drug effects
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HIV Antibodies / immunology
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HIV Envelope Protein gp41 / chemistry
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HIV Envelope Protein gp41 / metabolism*
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HIV-1 / drug effects*
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HIV-1 / physiology
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Humans
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Membrane Fusion / drug effects*
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Molecular Sequence Data
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Neutralization Tests
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Peptide Fragments / chemistry
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Peptides*
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Protein Conformation
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Protein Folding
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Protein Structure, Secondary
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Recombinant Proteins
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Tumor Cells, Cultured
Substances
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5-helix protein, synthetic
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Anti-HIV Agents
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Carrier Proteins
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HIV Antibodies
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HIV Envelope Protein gp41
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Peptide Fragments
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Peptides
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Recombinant Proteins