Abstract
Recombinant protein containing one heptad-repeat 1 (HR1) segment and one HR2 segment of the HIV-1 gp41 (HR1-HR2) has been shown to fold into thermally stable six-helix bundle, representing the fusogenic core of gp41. In this study, we have used the fusogenic core as a scaffold to design HIV-1 fusion inhibitory proteins by linking another HR1 to the C terminus of HR1-HR2 (HR121) or additional HR2 to the N terminus of HR1-HR2 (HR212). Both recombinant proteins could be abundantly and solubly expressed and easily purified, exhibiting high stability and potent inhibitory activity on HIV-1 fusion with IC50 values of 16.2+/-2.8 and 2.8+/-0.63 nM, respectively. These suggest that these rationally designed proteins can be further developed as novel anti-HIV-1 therapeutics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology*
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Drug Design
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HIV Envelope Protein gp41 / chemistry
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HIV Envelope Protein gp41 / genetics
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HIV Envelope Protein gp41 / physiology
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HIV-1 / drug effects*
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HIV-1 / pathogenicity
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HIV-1 / physiology*
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Humans
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In Vitro Techniques
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Membrane Fusion / drug effects
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Molecular Sequence Data
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Protein Engineering
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / pharmacology
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Viral Fusion Proteins / antagonists & inhibitors*
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Viral Fusion Proteins / chemistry
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Viral Fusion Proteins / genetics
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Viral Fusion Proteins / physiology
Substances
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Anti-HIV Agents
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HIV Envelope Protein gp41
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Recombinant Fusion Proteins
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Viral Fusion Proteins