Heptapeptide ligands against receptor-binding sites of influenza hemagglutinin toward anti-influenza therapy

Teruhiko Matsubara, Ai Onishi, Daisuke Yamaguchi, Toshinori Sato

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


The initial attachment of influenza virus to cells is the binding of hemagglutinin (HA) to the sialyloligosaccharide receptor; therefore, the small molecules that inhibit the sugar-protein interaction are promising as HA inhibitors to prevent the infection. We herein demonstrate that sialic acid-mimic heptapeptides are identified through a selection from a primary library against influenza virus HA. In order to obtain lead peptides, an affinity selection from a phage-displayed random heptapeptide library was performed with the HAs of the H1 and H3 strains, and two kinds of the HA-binding peptides were identified. The binding of the peptides to HAs was inhibited in the presence of sialic acid, and plaque assays indicated that the corresponding N-stearoyl peptide strongly inhibited infections by the A/Aichi/2/68 (H3N2) strain of the virus. Alanine scanning of the peptides indicated that arginine and proline were responsible for binding. The affinities of several mutant peptides with single-amino-acid substitutions against H3 HA were determined, and corresponding docking studies were performed. A Spearman analysis revealed a correlation between the affinity of the peptides and the docking study. These results provide a practicable method to design of peptide-based HA inhibitors that are promising as anti-influenza drugs.

Original languageEnglish
Pages (from-to)1106-1114
Number of pages9
JournalBioorganic and Medicinal Chemistry
Issue number5
Publication statusPublished - 2016 Mar 1


  • Hemagglutinin
  • Heptapeptide library
  • Peptide drug
  • Phage display
  • Sialic acid-mimic

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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