Division of Materials Science, Graduate School of Science and Technology, Saitama University , 255 Shimo-Ohkubo, Sakura-ku, Saitama 338-8570, Japan.
J Med Chem. 2014 Oct 23;57(20):8332-9. doi: 10.1021/jm5007676. Epub 2014 Oct 6.
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 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.
一系列均匀官能化的血凝集素（HA）结合肽（唾液酸模拟肽，Ala-Arg-Leu-Pro-Arg）的碳硅烷树状大分子被系统地合成，并评估了它们的抗流感病毒活性。与唾液酸化的树状大分子不同，基于碳硅烷的肽树状大分子不能被病毒神经氨酸酶消化。肽树状大分子表现出有趣的生物学活性，这取决于它们的核心框架的形式，哑铃型肽树状大分子对两种人类流感病毒 A/PR/8/34（H1N1）和 A/Aichi/2/68（H3N2）表现出特别强的抑制活性。哑铃型肽树状大分子对两种菌株的 IC50 值均为 0.60 μM，是 HA 结合肽衍生物中活性最高的。结果表明，哑铃形碳硅烷树状大分子是最适合 HA 结合肽树状大分子的核心支架。
