Preparation of glycopolymers having sialyl α2 → 3 lactose moieties as the potent inhibitors for mumps virus

Koji Matsuoka; Takayuki Kaneshima; Ryota Adachi; Jiei Sasaki; Takao Hashiguchi; Tetsuo Koyama; Takahiko Matsushita; Ken Hatano

doi:10.1016/j.bmcl.2021.128389

Preparation of glycopolymers having sialyl α2 → 3 lactose moieties as the potent inhibitors for mumps virus

Bioorg Med Chem Lett. 2021 Nov 15:52:128389. doi: 10.1016/j.bmcl.2021.128389. Epub 2021 Sep 30.

Authors

Koji Matsuoka¹, Takayuki Kaneshima², Ryota Adachi², Jiei Sasaki³, Takao Hashiguchi³, Tetsuo Koyama², Takahiko Matsushita⁴, Ken Hatano⁴

Affiliations

¹ Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan; Medical Innovation Research Unit (MiU), Advanced Institute of Innovative Technology (AIIT), Saitama University, Sakura, Saitama 338-8570, Japan. Electronic address: koji@fms.saitama-u.ac.jp.
² Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan.
³ Department of Virology, Faculty of Medicine, Kyushu University, Higashi, Fukuoka 812-8582, Japan.
⁴ Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan; Medical Innovation Research Unit (MiU), Advanced Institute of Innovative Technology (AIIT), Saitama University, Sakura, Saitama 338-8570, Japan.

PMID: 34600036
DOI: 10.1016/j.bmcl.2021.128389

Abstract

A water-soluble glycomonomer having a sialyl α2 → 3 lactose (SLac) moiety was prepared from a known imidate derivative of the SLac and an acrylamide alcohol by means of Schmidt's protocol followed by transesterification. Polymerization of the monomer proceeded in water as the solvent in the presence of ammonium persulfate (APS)-tetramethylethylenediamine (TEMED). Since acryl amide (AAm) was used as a regulator for the arrangement of sugar density, three kinds of glycopolymers having different sugar densities were obtained. Infection inhibition assays of mumps virus (MuV) for Vero cells using the glycopolymers were performed, and the results showed that a glycopolymer having a low sugar density has the highest inhibitory potency. In comparison to sialyl Lewis X (SLe^X) as the strongest inhibitor in a previous study, SLac polymer with the low sugar density showed ten-times stronger inhibitory potency than that of SLe^x. This finding suggested that multivalent conversion of the monomeric SLac with appropriate spatial arrangement are able to effectively inhibit the interaction between the attachment glycoprotein of MuV and glycan receptors on Vero cells.

Keywords: Glycoclusters; Glycopolymers; Inhibitors; Mumps viruses; Radical polymerization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Chlorocebus aethiops
Dose-Response Relationship, Drug
Lactose / chemistry
Lactose / pharmacology*
Molecular Structure
Mumps virus / drug effects*
Polymers / chemical synthesis
Polymers / chemistry
Polymers / pharmacology*
Structure-Activity Relationship
Vero Cells

Substances

Antiviral Agents
Polymers
Lactose