Protecting-Group-Free Synthesis of Glycopolymers Bearing Sialyloligosaccharide and Their High Binding with the Influenza Virus

Abstract

Glycopolymers having pendant triazole-linked sialyloligosaccharides were successfully synthesized from free saccharides without any protection of the hydroxy and carboxy groups on the saccharides. The glycomonomers were synthesized by the direct azidation of free saccharides using 2-chloro-1,3dimethylimidazolinium chloride as a condensing agent followed by copper(I)-catalyzed azide−alkyne cycloaddition. The resultant glycomonomers were copolymerized with acrylamide by a reversible addition−fragmentation chain transfer technique. Each of the glycopolymers were obtained and then immobilized on a gold-coated sensor of quartz crystal microbalance to analyze their binding behavior with the lectin. The glycopolymers strongly bound with the corresponding lectin without nonspecific adsorption in aqueous solution. In addition, the glycopolymer bearing a complex-type sialyl N-linked oligosaccharide was found to strongly bind with both human and avian influenza A viruses. The strong binding, observed using the hemagglutination inhibition assay, was attributed to the glycocluster effect of the glycopolymer and the biantennary structure of the N-linked oligosaccharide.

Multivalent Sialosides: A Tool to Explore the Role of Sialic Acids in Biological Processes

“…However, such functionalization of higher oligosaccharides is laborious and requires multistep syntheses. To get around this problem, Kimura and co‐workers combined the copper(I)‐mediated click reaction with an acrylate‐polymerization strategy and synthesized sialo‐oligosaccharide copolymers (Figure a) . These sialo‐polymers (Neu5Acα(2–3)galβ(1–4)gal, sialylated N ‐glycan) were functionalized on a quartz crystal microbalance (QCM) to study their binding affinity with influenza viruses.…”

“…To get around this problem, Kimura and co-workers combined the copper(I)-mediated click reactionw ith an acrylate-polymerization strategy and synthesized sialo-oligosaccharide copolymers ( Figure 2a). [31] These sialo-polymers( Neu5Aca(2-3)galb(1-4)gal, sialylated N-glycan) were functionalized on a quartz crystal microbalance (QCM) to study their binding affinity with influenza viruses.T he sialylated N-glycanp olymer was found to exhibit stronger binding with human and avian influenza Av iruses compared to the Neu5Ac-polymer,w hich was attributed to multivalency and synergistic effects of the higher-oligosaccharidet oa fford sensitivev irus-protein recognition.…”

Synthesis of Glycopolymer Gold Nanoparticles Decorated with Oligosaccharides via a Protecting-group-free Process and Their Specific Recognition by Lectins

“…[18] These glycopolymers were immobilized on GNPs by Au-S bond formation after reducing the trithiocarbonate terminal group with sodium borohydride. When peanut agglutinin from Arachis hypogaea (PNA) was added to a suspension of PolyLacAAm-immobilized GNPs (PolyLacAAm-GNPs), the absorption at 530 nm gradually decreased with increasing concentration of PNA from 0 to 100 nM due to specific recognition by PNA of the β-galactosyl residue (the nonreducing-end monosaccharide moiety in Lac) (Fig.…”

“…Finally, the product was purified by ion-exchange column chromatography (Amberlite IR-120B, previously activated with 1 M NaOH, eluent; H2O) and concentrated under reduced pressure to give a β-glycosyl azide. [18,20] 4.4 Synthesis of glycomonomers Glc2AAm. N-Propargyl acrylamide (200 mg, 1.83 mmol), CuSO45H2O (100 mg, 0.398 mmol), AscNa (158 mg, 0.798 mmol), and TBTA (72 mg, 0.136 mmol) were added to a 50% DMF aqueous solution (6.6 mL) of -maltosyl azide (460 mg, 1.25 mmol), and the resulting mixture was stirred for 3.5 h at room temperature.…”

“…[18,19] We followed the reversible addition-fragmentation chain transfer (RAFT) polymerization reaction using the resulting glycomonomers to obtain glycopolymers. In this paper, we report the decoration of gold nanoparticles (GNPs) using glycopolymers bearing oligosaccharides, and investigate the binding properties of lectins towards the glycopolymer-decorated GNPs.…”