Synthesis and influenza virus inhibitory activities of carbosilane dendrimers peripherally functionalized with hemagglutinin-binding peptide

Ken Hatano, Teruhiko Matsubara, Yosuke Muramatsu, Masakazu Ezure, Tetsuo Koyama, Koji Matsuoka, Ryunosuke Kuriyama, Haruka Kori, Toshinori Sato

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

A series of carbosilane dendrimers uniformly functionalized with hemagglutinin (HA) binding peptide (sialic acid-mimic peptide, Ala-Arg-Leu-Pro-Arg) was systematically synthesized, and their anti-influenza virus activity was evaluated. The carbosilane-based peptide dendrimers, unlike sialylated dendrimers, cannot be digested by virus neuraminidases. The peptide dendrimers exhibited intriguing biological activities depending on the form of their core frame, with a dumbbell-type peptide dendrimer showing particularly strong inhibitory activities against two human influenza viruses, A/PR/8/34 (H1N1) and A/Aichi/2/68 (H3N2). The IC<inf>50</inf> values of the dumbbell-type peptide dendrimer for both strains were 0.60 μM, the highest activity among the HA-binding peptide derivatives. The results suggest that a dumbbell-shaped carbosilane dendrimer is the most suitable core scaffold for HA-binding peptide dendrimers.

Original languageEnglish
Pages (from-to)8332-8339
Number of pages8
JournalJournal of Medicinal Chemistry
Volume57
Issue number20
DOIs
Publication statusPublished - 2014 Oct 23

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Dendrimers
Hemagglutinins
Orthomyxoviridae
Peptides
Sialic Acid Binding Immunoglobulin-like Lectins
carbosilane
Neuraminidase
Human Influenza
Inhibitory Concentration 50
Viruses

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Medicine(all)

Cite this

Synthesis and influenza virus inhibitory activities of carbosilane dendrimers peripherally functionalized with hemagglutinin-binding peptide. / Hatano, Ken; Matsubara, Teruhiko; Muramatsu, Yosuke; Ezure, Masakazu; Koyama, Tetsuo; Matsuoka, Koji; Kuriyama, Ryunosuke; Kori, Haruka; Sato, Toshinori.

In: Journal of Medicinal Chemistry, Vol. 57, No. 20, 23.10.2014, p. 8332-8339.

Research output: Contribution to journalArticle

Hatano, Ken ; Matsubara, Teruhiko ; Muramatsu, Yosuke ; Ezure, Masakazu ; Koyama, Tetsuo ; Matsuoka, Koji ; Kuriyama, Ryunosuke ; Kori, Haruka ; Sato, Toshinori. / Synthesis and influenza virus inhibitory activities of carbosilane dendrimers peripherally functionalized with hemagglutinin-binding peptide. In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 20. pp. 8332-8339.
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