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

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.