Sialic acid-mimic peptides as hemagglutinin inhibitors for anti-influenza therapy

Teruhiko Matsubara, Ai Onishi, Tomomi Saito, Aki Shimada, Hiroki Inoue, Takao Taki, Kyosuke Nagata, Yoshio Okahata, Toshinori Sato

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Influenza is an infectious disease caused by the influenza virus, and each year many people suffer from this disease. Hemagglutinin (HA) in the membrane of type A influenza viruses recognizes sialylglycoconjugate receptors on the host cell surface at an initial step in the infection process; consequently, HA inhibitors are considered potential candidates for antiviral drugs. We identified peptides that bind to receptor-binding sites through a multiple serial selection from phage-displayed random peptide libraries. Using the HA of the H1 and H3 strains as target proteins, we obtained peptides that bind to both HAs. The binding affinities of peptides for these HAs were improved by secondary and tertiary selections from the corresponding sublibraries. A docking simulation suggested that, similar to sialic acid, the peptides are recognized by the receptor-binding site in HA, which indicates that these peptides mimic the sialic acid structure. N-stearoyl peptides inhibited infections by the A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/68 (H3N2) strains of influenza virus. Such HA-inhibitors are promising candidates for novel antiviral drugs.

Original languageEnglish
Pages (from-to)4441-4449
Number of pages9
JournalJournal of Medicinal Chemistry
Volume53
Issue number11
DOIs
Publication statusPublished - 2010 Jun 10

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Matsubara, T., Onishi, A., Saito, T., Shimada, A., Inoue, H., Taki, T., Nagata, K., Okahata, Y., & Sato, T. (2010). Sialic acid-mimic peptides as hemagglutinin inhibitors for anti-influenza therapy. Journal of Medicinal Chemistry, 53(11), 4441-4449. https://doi.org/10.1021/jm1002183