Synthetic Glycosidase Distinguishing Glycan and Glycosidic Linkage in Its Catalytic Hydrolysis

Selective hydrolysis of carbohydrates is vital to the processing of these molecules in biology but has rarely been achieved with synthetic catalysts. The challenge is especially difficult because the catalyst needs to distinguish the inversion of a single hydroxyl and the alpha or beta glycosidic bonds that join monosaccharide building blocks. Here, we report synthetic glycosidase prepared through molecular imprinting within a cross-linked micelle. The nanoparticle catalyst resembles natural enzymes in dimension, water solubility, and a hydrophilic/hydrophobic surface-core topology. Its boronic acid functionalized active site binds its targeted glycoside substrate and an acid cofactor simultaneously, with the acidic group in close proximity to the exocyclic glycosidic oxygen. The hydrophobically anchored acid cofactor is tunable in acidity and causes selective cleavage of the targeted glycoside in mildly acidic water. Selectivity for both the glycan and the alpha/beta glycosidic bond can be rationally designed through the molecular imprinting process.