Novel recombinant engineered gp41 N-terminal heptad repeat trimers and their potential as anti-HIV-1 therapeutics or microbicides.
Peptides derived from N-terminal heptad repeat (NHR) of the HIV-1 gp41 are generally poor inhibitors of HIV-1 entry, because they tend to aggregate and do not form a trimeric coiled-coil. In this study, we have fused portions of gp41 NHR, e.g. N36 or N28, to the T4 fibritin trimerization domain, Foldon (Fd), thus constructing novel NHR trimers, designated N36Fd or N28Fd, which could be expressed in Escherichia coli cells. The purified N36Fd and N28Fd exhibited SDS-resistant trimeric coiled-coil conformation with improved alpha-helicity compared with the corresponding N-peptides. They could interact with a C-peptide (e.g. C34) to form stable six-helix bundle and possessed potent anti-HIV-1 activity against a broad spectrum of HIV-1 strains. N28Fd was effective against T20-resistant HIV-1 variants and more resistant to proteinase K compared with T20 (enfuvirtide), a C-peptide-based HIV fusion inhibitor. Therefore, N28Fd trimer has great potentials for further development as an affordable therapeutic or microbicide for treatment and prevention of HIV-1 infection.
Chen
Xi
X
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Lu
Lu
L
Qi
Zhi
Z
Lu
Hong
H
Wang
Ji
J
Yu
Xiaoxia
X
Chen
Yinghua
Y
Jiang
Shibo
S
D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins; C514787:gp41 protein, Human immunodeficiency virus 1