Title

Biomimetic Glycoside Hydrolysis by a Microgel Templated with a Competitive Glycosidase Inhibitor

Document Type

Article

Publication Date

2018

Keywords

galactonoamidines, glycosides, hydrolysis, macromolecular catalyst, matrix effects, polyacrylate microgels, transition state analogue

Abstract

The impressive catalytic turnover and selectivity of biological catalysts instigated a tremendous effort to understand the source of this catalytic proficiency. In this regard, the synthesis and evaluation of biomimetic catalysts is a very valuable approach to gain insights into the enzymatic mechanisms of action. In addition, anticipated key interactions of the enzymatic turnover can be implemented into enzyme mimics to probe their contributions to the overall catalytic efficiency separately. In this context, we synthesized biomimetic microgels in the presence of an experimentally identified competitive glycosidase inhibitor and evaluated the resulting macromolecular catalysts for proficiency during glycoside hydrolyses. The stepwise-built microgels utilize a synergy of interactions including metal complex catalysis in a hydrophobic microgel matrix, cross-linking, and shape recognition for a glyconoamidine model of the transition state of the enzymatically catalyzed glycoside hydrolyses. The resulting microgels show biomimetic behavior including catalytic proficiency up to 3.3 × 106 in alkaline and 1 × 107 in neutral aqueous solution: independence of catalytic sites, competitive inhibition, and an inhibition constant Ki of 100 μM in 5 mM HEPES buffer (pH 7.00). Our results place the synthesized microgels among the most proficient biomimetic catalysts known and emphasize the synergy of interactions for an advanced catalytic turnover.

Comments

The authors thank Peter Pulay for advice and access to PQSmol. Support of this research to S.S. from the Arkansas Biosciences Institute and in part from the National Science Foundation (CHE-1305543) is gratefully acknowledged.

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