Programmable Monodisperse Glyco-Multivalency Using Self-Assembled Coordination Cages as Scaffolds

The multivalent presentation of glycans leads to enhancedbindingavidity to lectins due to the cluster glycoside effect. Most materialsused as scaffolds for multivalent glycan arrays, such as polymersor nanoparticles, have intrinsic dispersity: meaning that in any sample,a range of valencies are presented and it is not possible to determinewhich fraction(s) are responsible for binding. The intrinsic dispersityof many multivalent glycan scaffolds also limits their reproducibilityand predictability. Here we make use of the structurally programmablenature of self-assembled metal coordination cages, with polyhedralmetal-ion cores supporting ligand arrays of predictable sizes, toassemble a 16-membered library of perfectly monodisperse glycoclustersdisplaying valencies from 2 to 24 through a careful choice of ligand/metalcombinations. Mono- and trisaccharides are introduced into these clusters,showing that the synthetic route is tolerant of biologically relevantglycans, including sialic acids. The cluster series demonstrates increasedbinding to a range of lectins as the number of glycans increases.This strategy offers an alternative to current glycomaterials forcontrol of the valency of three-dimensional (3-D) glycan arrays, andmay find application across sensing, imaging, and basic biology.

Automated summary

The presentation of glycans in multiple forms enhances their binding capacity to lectins. Current materials used as scaffolds for multivalent glycan arrays have limited reproducibility and predictability due to their intrinsic dispersity. In this study, self-assembled metal coordination cages with predictable ligand arrays were used to assemble a monodisperse library of glycoclusters displaying a range of valencies. The synthetic route was tolerant of biologically relevant glycans, and the glycocluster series demonstrated increased binding to lectins with increasing glycans. This strategy offers an alternative for controlling the valency of 3-D glycan arrays and has potential applications in sensing, imaging, and basic biology.