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

Abstract

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.

Design of Glycopolymers for Controlling the Interactions with Lectins

“…Furthremore, inspired by the research on glyco-ligands aiming to achieve the multivalent binding to the three CRDs of hemagglutinin using DNA and peptides, [25,26] our group synthesized tri-arm star glycopolymers. [27,28] 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 the three CRDs of hemagglutinin was estimated (Figure 2). [28] The disance between the two CRDs of hemagglutinin is ca.…”

“…[27,28] 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 the three CRDs of hemagglutinin was estimated (Figure 2). [28] The disance between the two CRDs of hemagglutinin is ca. 2.6 nm, and the corresponding degree of polymerization was 40.…”

“…In this work, they revealed that both of the polymer length which is sufficient to form multivalent binding with hemagglutinin and of the appropriate glycounit density which avoid the steric hindrance of the trisaccharide side chains are important for the strong interactions with the influenza viruses. Furthremore, inspired by the research on glyco‐ligands aiming to achieve the multivalent binding to the three CRDs of hemagglutinin using DNA and peptides, [25,26] our group synthesized tri‐arm star glycopolymers [27,28] . 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 the three CRDs of hemagglutinin was estimated (Figure 2).…”

Discovering Neuraminidase Inhibitors via Computational and Experimental Studies

“…New strains of the viruses continue to emerge and the risk of drug resistance have sparked great interest into finding potential anti-viral compounds. [9][10][11][12][13][14][15] Neuraminidase is a key surface glycoprotein which plays an important role in viral replication and infection. It is a proven target for developing drugs against influenza A viruses [16][17] .…”

MedChemExpress compounds prevent neuraminidase N1 via physics- and knowledge-based methods

“…Numerous studies were carried out to nd a potential inhibitor for treating the disease. [9][10][11][12][13][14][15] In particular, neuraminidase is the most popular drug target since it is an important element in the delivery of viral progeny to human cells. 16 Oseltamivir, zanamivir, and peramivir are among the drugs approved for inhibiting the target.…”