Optimal glycan density for interactions between Siglec-8 and sialyl sulfo oligosaccharides

Abstract

AbstractSiglec-8, a lectin involved in the suppression of allergic responses, is considered a therapeutic target for developing glycan materials that enable the regulation of inflammatory diseases. In developing such glycan materials, the “multivalent effect” is essential for regulating immune responses. The “multivalent effect” dramatically increases the apparent affinities (avidities) of glycan-lectin interactions by clustering the glycan ligand multivalently. Numerous lectin-glycan interactions utilize this effect in immunological reactions, and Siglec-8 is thought to show an effect similar to those of other lectins. However, we hypothesized that increasing the local concentration of glycan ligands and modulating the glycan density are essential in allowing glycan ligands to interact effectively with Siglec-8. Here, we investigate the density-dependent changes in avidities between Siglec-8 and sialyl sulfo-oligosaccharides with a quartz crystal microbalance (QCM) for the first time. As a result, it was determined that Siglec-8 has an optimal glycan density (~9.2 × 102 molecules μm−2) for preferred interactions. Additionally, this suggests that the regulation of glycan density is key to developing therapeutic materials targeting Siglec-8. The results described here will promote the development of glycan materials that ameliorate immune disorders such as inflammation and anaphylaxis.