4.7 Article

Synthesis and Influenza Virus Inhibitory Activities of Carbosilane Dendrimers Peripherally Functionalized with Hemagglutinin-Binding Peptide

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JOURNAL OF MEDICINAL CHEMISTRY
卷 57, 期 20, 页码 8332-8339

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AMER CHEMICAL SOC
DOI: 10.1021/jm5007676

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  1. Grants-in-Aid for Scientific Research [23241075] Funding Source: KAKEN

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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 IC50 values of the dumbbell-type peptide dendrimer for both strains were 0.60 mu M, 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.

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