title: Potent anti-HIV-1 activity of N-HR-derived peptides including a deep pocket-forming region without antagonistic effects on T-20.
abstract: BACKGROUND
  Enfuvirtide (T-20), a C-terminal heptad repeat (C-HR)-derived peptide of HIV-1 glycoprotein, gp41, effectively suppresses HIV-1 replication through a putative mechanism that involves it acting as a decoy and binding to the N-terminal heptad repeat (N-HR) of the virus. In this study, we address whether the anti-HIV-1 activity of T-20 is antagonized by a variety of N-HR-derived peptides.
  
  
  METHODS
  Multinuclear activation of galactosidase indicator assays were used to evaluate T-20 activity in the presence of N-HR-derived peptides. The gp41-derived peptides were chemically synthesized.
  
  
  RESULTS
  We demonstrate additive anti-HIV activity when T-20 is used in combination with N-HR-derived peptides that do not have a putative binding region for the tryptophan-rich domain in T-20. The presence of a deep pocket-forming region in the N-HR-derived peptides enhanced their anti-HIV-1 activity, but had little effect on the activity of T-20.
  
  
  CONCLUSIONS
  These results indicate that T-20-based antiviral therapies can be combined with N-HR-derived peptides.
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Department of Bioorganic Medical Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Izumi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Sarafianos
authors.forename: Eiichi N
authors.initials: EN
authors.lastname: Kodama
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D004357:Drug Synergism; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D010455:Peptides; D000077560:Enfuvirtide