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

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• 作者：Ken Hatano ; Teruhiko Matsubara ; Yosuke Muramatsu ; Masakazu Ezure ; Tetsuo Koyama ; Koji Matsuoka ; Ryunosuke Kuriyama ; Haruka Kori ; Toshinori Sato
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：October 23, 2014
• 年：2014
• 卷：57
• 期：20
• 页码：8332-8339
• 全文大小：334K
• ISSN：1520-4804

文摘

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 渭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.