Natural glycoside hydrolases are distinguished by their ability to hydrolyze glycosidic bonds with high efficiency and selectivity. This feature is achieved through specific interactions in the active site during catalytic turnover and is not just facilitated by two catalytically active amino acids. Intrigued by these features, a biomimetic α-galactosidase mimic was developed using an empirical catalyst design. Starting with a library of 704 gels of which 250 have a unique composition synthesized from TEGDMA cross-linker and 7 selected monomers, 238 monomodal gels are evaluated for their ability to hydrolyze the 1→6 αglycosidic bond in the disaccharide melibiose. Among those, 13 polyacrylate gels with the potential for high catalytic activity are identified using spectrophotometric screening assays based on Schiff bases formed with toluidine. The best-performing polyacrylate (gel A) was found to have a 1500-fold higher proficiency to hydrolyze the 1→6 αglycosidic bond in melibiose over the 1→2 α-glycosidic bond in sucrose, translating to selective hydrolysis of the glycosidic linkages in the trisaccharide raffinose. The matrix of gel A is composed of 25 mol % TEGDMA cross-linker and equimolar amounts of cyclohexyl, butyl, and benzyl acrylate accounting for CH-π and hydrophobic interaction in the surrounding of a hydrolytic binuclear Cu(II) complex. The combined observations underline a paramount influence of matrix-stabilizing effects on the transition state of the hydrolysis of glycosidic bonds and may pave the way for the rapid development of catalysts transforming biomass.
