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

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 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.

Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases

“…Hatano and co-workers synthesized a series of carbosilane dendrimers with hemagglutinin binding peptide and evaluated their activity against influenza virus. The prepared dendrimers were found to exhibit strong anti-viral activity against human viruses [89]. Dendrimeric nanomaterials were prepared by chemical modifications and then optimized for targeted delivery of small interfering RNA (siRNA) to pulmonary vasculature.…”

Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding

“…Recently, we demonstrated that the antiviral effectivity of acylated PeB GF can be increased, upon presentation in a multivalent fashion by 10-fold against Rostock H7N1 and by 20-fold against Aichi H3N2 [60]. Further, multivalent presentation of the short s2 peptide (ARLPR) with a dendrimer resulted in sub-micromolar inhibitory activities [61].…”

Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition

“…Thereafter, a peptide was optimized for HA binding by selection from a phage‐displayed random peptide library 24. This work also showed a multivalent improvement of its binding properties by conjugation to either an amphiphilic N ‐stearoyl derivative, which formed self‐assembled multivalent structures with enhanced binding capabilities or by presenting up to six peptide copies on a carbosilane dendrimer 24, 30, 31…”