Dissecting Multivalent Carbohydrate Binding through Controlled Ligand Patterns on Cyclic Nanoscaffolds
Journal
Biomacromolecules
Journal Volume
27
Journal Issue
5
Start Page
3199
End Page
3209
ISSN
1525-7797
1526-4602
Date Issued
2026-04-24
Author(s)
Wang, Xin-Yu
Lee, Zong-You
Li, Meng-Che
Hashimoto, Masayuki
Cheung, Kwun-Yung
Cheng, Wei-Chieh
Wang, Sheng-Kai
Abstract
Carbohydrate–protein interactions are essential for biological recognition but often suffer from cross-reactivity. Multivalency can enhance the binding strength; however, it requires a precise spatial arrangement of carbohydrate ligands to match the protein binding sites. Controlling glycan presentation improves both avidity and selectivity, helping to reduce cross-reactivity. However, complex proteins, such as AB5-type Shiga toxin (Stx), present additional challenges, as the B subunits form pentamers, and each subunit contains three nonequivalent glycan-binding sites. To address this, we developed oligoproline-based cyclic nanoscaffolds and characterized them by using circular dichroism and ion-mobility spectrometry. Surface plasmon resonance analysis showed that different glycan patterns on these scaffolds produced distinct binding modes with the StxB pentamer. By coupling a fully tunable synthetic nanoscaffold platform with analytical methods capable of resolving complex binding behaviors, this work enables a deeper investigation of protein receptors and supports the design of more selective multivalent biomolecules.
Publisher
American Chemical Society (ACS)
Type
journal article