De Novo Design of Star-Shaped Glycoligands with Synthetic Polymer Structures toward an Influenza Hemagglutinin Inhibitor

Synthetic polymers with well-defined structures allow the development of nanomaterials with additional functions beyond biopolymers. Herein, we demonstrate de novo design of star-shaped glycoligands to interact with hemagglutinin (HA) using well-defined synthetic polymers with the aim of developing an effective inhibitor for the influenza virus. Prior to the synthesis, the length of the star polymer chains was predicted using the Gaussian model of synthetic polymers, and the degree of polymerization required to achieve multivalent binding to three carbohydrate recognition domains (CRDs) of HA was estimated. The star polymer with the predicted degree of polymerization was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, and 6'-sialyllactose was conjugated as the glycoepitope for HA. The designed glycoligand exhibited the strongest interaction with HA as a result of multivalent binding. This finding demonstrated that the biological function of the synthetic polymer could be controlled by precisely defining the polymer structures.

Automated summary

Synthetic polymers with precise structures were used to design star-shaped glycoligands that interacted with hemagglutinin (HA) for developing an effective inhibitor for the influenza virus. The designed glycoligand showed strong interaction with HA due to multivalent binding, demonstrating that biological function of synthetic polymers can be controlled by defining polymer structures precisely.