title: Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs.
abstract: The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins.
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, Pharmaceutical Chemistry, 27 Taiping Road, Beijing 100850, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Shi
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
authors.forename: Chungen
authors.initials: C
authors.lastname: Pan
authors.forename: Na
authors.initials: N
authors.lastname: Xue
authors.forename: Asim K
authors.initials: AK
authors.lastname: Debnath
authors.forename: Jiankun
authors.initials: J
authors.lastname: Qie
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Keliang
authors.initials: K
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D002459:Cell Fusion; D015195:Drug Design; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C407149:peptide C34; C407148:peptide N36; D000077560:Enfuvirtide