Developing Catalysts\nfor the Hydrolysis of Glycosidic\nBonds in Oligosaccharides Using a Spectrophotometric Screening Assay

In a proof-of-concept study, a method for the empirical\ndesign\nof polyacrylate gel catalysts with the ability to cleave 1→4\nα-glycosidic bonds in di- and trisaccharides was elaborated.\nThe study included the synthesis of a 300-gel member library based\non two different cross-linkers and 10 acrylate monomers, identification\nof monomodal gels by dynamic light scattering, and a 96-well plate\nspectrophotometric screening assay to monitor the hydrolysis of chromophore-free\nmaltose into glucose units. The composition of the matrix of the most\nefficient catalysts in the library was found to enable CH−π,\nhydrophobic, and H-bond accepting interactions during the hydrolysis\nas typically seen in glycosylases. The same gel catalysts allowed\nthe hydrolysis of the trisaccharide maltotriose with a catalytic proficiency\nof 2 × 10<sup>6</sup> indicating transition state stabilization\nduring the hydrolysis of 5 × 10<sup>–7</sup>. The results\nplace the developed gels among the most efficient catalysts developed\nfor the hydrolysis of natural saccharides. The elaborated strategy\nmay lead to catalysts that can transform polysaccharides into valuable\nsynthons in the near future.