Dynamic Tuning in Synthetic Glycosidase for Selective Hydrolysis of Alkyl and Aryl Glycosides.

Enzymes use sophisticated conformational control to optimize the dynamics of their protein framework for efficient catalysis. Although it is difficult to employ a similar strategy to improve catalysis in a synthetic enzyme, we here report that modulation of the dynamics of the substrate in the active site is readily achievable in a complex between a molecularly imprinted nanoparticle and its acid cofactor, through tuning of the size and shape of the imprinted site. As the alkyl glucoside substrate is bound with increasing strength and held in a more tightly fitted pocket, the acid-catalyzed glycan hydrolysis becomes more difficult. A larger, wider active site, although less able to bind the substrate, affords a higher catalytic activity, likely due to easier alignment of the substrate and the acid cofactor for a general acid catalysis. The substrate selectivity is controlled by both the tightness of the aglycon-binding site and the orientation of the glycan-binding boroxole group.