Work

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

Year: 2026

Type: article

Abstract: 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.

Source: Communications Chemistry

DOI: 10.1038/s42004-026-02228-8

Authors: Emerson Hall, Yu-Shien Sung, Chad W. Priest, Julia M. Stauber, Alex J. Guseman

Institution: University of California San Diego

Language: English

Topic: Carbohydrate Chemistry and Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $3,690

Funders: National Institutes of Health, University of California, San Diego, National Cancer Institute, National Institute of General Medical Sciences