title: Rational design of highly potent HIV-1 fusion inhibitory proteins: implication for developing antiviral therapeutics.
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.
authors.affiliation: Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ni
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.forename: Po
authors.initials: P
authors.lastname: Tien
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008561:Membrane Fusion / Q000187:drug effects; D008969:Molecular Sequence Data; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D014760:Viral Fusion Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000502:physiology
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins