Structural control of Fe(II)-based multivalent glycan assemblies enables intramolecular avidity and ultra-high-affinity binding
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.
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BibTeX
@article{hall2026structural,
title = {{Structural control of Fe(II)-based multivalent glycan assemblies enables intramolecular avidity and ultra-high-affinity binding}},
author = {Emerson Hall and Yu-Shien Sung and Chad W. Priest and Julia M. Stauber and Alex J. Guseman},
journal = {Communications Chemistry},
year = {2026},
month = oct,
doi = {10.1038/s42004-026-02228-8},
url = {https://www.nature.com/articles/s42004-026-02228-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Structural control of Fe(II)-based multivalent glycan assemblies enables intramolecular avidity and ultra-high-affinity binding
AU - Emerson Hall
AU - Yu-Shien Sung
AU - Chad W. Priest
AU - Julia M. Stauber
AU - Alex J. Guseman
PY - 2026
DA - 2026/10/15
JO - Communications Chemistry
DO - 10.1038/s42004-026-02228-8
UR - https://www.nature.com/articles/s42004-026-02228-8
AB - 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.
SN - 2399-3669
ER -