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Rational design of highly potent HIV-1 fusion inhibitory proteins: Implication for developing antiviral therapeutics

2005; Elsevier BV; Volume: 332; Issue: 3 Linguagem: Inglês

10.1016/j.bbrc.2005.05.037

1090-2104

Ling Ni, George F. Gao, Po Tien,

Monoclonal and Polyclonal Antibodies Research

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.