The role of water in controlling molecular recognition of glycopolymers

Water is indispensable for life and plays a central role in biological functions. However, the role of water has received relatively little attention in the context of biomolecular interactions (molecular recognition), despite these interactions being central to biological processes. In this study, glycopolymers with distinct backbones (acrylamide or acrylate) and linker lengths (methylene or ethylene) were synthesized via RAFT polymerization to investigate their hydration states. Thermal analysis revealed that glycopolymers with acrylamide backbones retained more hydration water than those with acrylate backbones. This trend was consistently supported by terahertz spectroscopy and molecular dynamics simulations. In addition, the amount of hydration water increased with increasing linker length. Hemagglutination inhibition assays showed that acrylate-based glycopolymers exhibited markedly higher binding affinity for concanavalin A than their acrylamide-based counterparts across all degrees of polymerization. Importantly, these results reveal a clear inverse correlation between the amount of hydration water and binding affinity, indicating that excessive hydration hinders lectin recognition.