Structural control of Fe(II)-based multivalent glycan assemblies enables intramolecular avidity and ultra-high-affinity binding

Multivalent glycan recognition depends critically on the spatial organization of saccharides, yet quantitative design rules linking glycan geometry to binding remain poorly defined. Here, we report atomically-precise Fe(II)-based glycoassemblies that enable independent control of glycan valency, spacing, and topology within discrete molecular scaffolds. Using monomeric Griffithsin as a model lectin, we uncover that subtle changes in glycan presentation drive discrete transitions from partial site engagement to high-avidity, multi-site binding, spanning a > 10³-fold range in affinity. Structurally optimized assemblies achieve binding that surpass the binding strength of native high-mannose glycans, entering an effectively irreversible regime. These findings define geometric thresholds for intramolecular avidity and establish a framework for engineering multivalent ligands with programmable binding properties.