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.