Sequence-Dependent Effects of Folded Glycopolymer Structures on Their Biomolecular Recognition

We demonstrate that folded polymer structures have distinct effects on their binding affinity to target biomolecules depending on the polymer sequence pattern. We synthesized random and triblock glycopolymers with either folded or non-folded structures in water. These glycopolymers contained mannose units as a biofunctional group, while di(phenylalanine) units were incorporated into the folded glycopolymers as hydrophobic segments to promote self-folding of the polymer chains in aqueous solution. We then evaluated the interactions of these glycopolymers with a model protein, concanavalin A (ConA), using isothermal titration calorimetry. The folded random glycopolymer exhibited a higher binding constant than its non-folded counterpart, whereas the opposite trend was observed in the triblock glycopolymer series. In both sequence patterns, further compaction of the polymer structures led to a decrease in binding affinity to ConA. These findings highlight the importance of the spatial arrangement of functional groups and polymer-chain flexibility in the design of functional polymers inspired by protein behavior.