Multivalent Binding of Precision Glycooligomers on Soft Glycocalyx Mimicking Hydrogels.

We present a synthetic approach toward soft, glycooligomer-functionalized microgel particles mimicking carbohydrate presenting cell surfaces and analyze their specific binding to a model lectin (Concanavalin A, ConA). Focusing on multivalent presentation, a series of sequence-controlled glycooligomers with varying spacing and number of mannose units was synthesized and analyzed for the resulting glycooligomer-ConA affinity. Both direct binding and inhibition studies show a higher affinity with increasing the number of sugar moieties, but they level off for higher valent systems, indicating steric hindrance. Furthermore, the results suggest that increasing the scaffold length tends to decrease binding due to entropic repulsion, which could be compensated by larger scaffolds able to address multiple ConA binding sites. These findings were consistent in all assays (adhesion, fluorescence, and ITC) regardless of binding partner immobilization, demonstrating that flexible ligands exert similar binding modes in solution and when attached to polymer networks, which is relevant for designing glyco-functionalized materials.