A DNA-Conjugated Small Molecule Catalyst Enzyme Mimic for Site-Selective Ester Hydrolysis

Moira L. Flanagan, Smith College
A. Emilia Arguello, Smith College
Drew E. Colman, Smith College
Jiyeon Kim, Smith College
Jesse N. Krejci, Smith College
Shimu Liu, Smith College
Yueyu Yao, Smith College
Yu Zhang, Smith College
David J. Gorin, Smith College

Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc04554a

Abstract

The challenge of site-selectivity must be overcome in many chemical research contexts, including selective functionalization in complex natural products and labeling of one biomolecule in a living system. Synthetic catalysts incorporating molecular recognition domains can mimic naturally-occurring enzymes to direct a chemical reaction to a particular instance of a functional group. We propose that DNA-conjugated small molecule catalysts (DCats), prepared by tethering a small molecule catalyst to a DNA aptamer, are a promising class of reagents for site-selective transformations. Specifically, a DNA-imidazole conjugate able to increase the rate of ester hydrolysis in a target ester by >100-fold compared with equimolar untethered imidazole was developed. Other esters are unaffected. Furthermore, DCat-catalyzed hydrolysis follows enzyme-like kinetics and a stimuli-responsive variant of the DCat enables programmable “turn on” of the desired reaction