Developing Catalysts for the Hydrolysis of Glycosidic Bonds in Oligosaccharides Using a Spectrophotometric Screening Assay

In a proof-of-concept study, a method for the empirical design of polyacrylate gel catalysts with the ability to cleave 1→4 α-glycosidic bonds in di- and trisaccharides was elaborated. The study included the synthesis of a 300-gel member library based on two different cross-linkers and 10 acrylate monomers, identification of monomodal gels by dynamic light scattering, and a 96-well plate spectrophotometric screening assay to monitor the hydrolysis of chromophore-free maltose into glucose units. The composition of the matrix of the most efficient catalysts in the library was found to enable CH−π, hydrophobic, and H-bond accepting interactions during the hydrolysis as typically seen in glycosylases. The same gel catalysts allowed the hydrolysis of the trisaccharide maltotriose with a catalytic proficiency of 2 × 106 indicating transition state stabilization during the hydrolysis of 5 × 10–7. The results place the developed gels among the most efficient catalysts developed for the hydrolysis of natural saccharides. The elaborated strategy may lead to catalysts that can transform polysaccharides into valuable synthons in the near future.