A DNA-conjugated small molecule catalyst enzyme mimic for site-selective ester hydrolysis

• Published in: Chemical science (Cambridge) 2018-02, Vol.9 (8), p.2105-2112
• Main Authors: Flanagan, Moira L, Arguello, A Emilia, Colman, Drew E, Kim, Jiyeon, Krejci, Jesse N, Liu, Shimu, Yao, Yueyu, Zhang, Yu, Gorin, David J
• Format: Article
• Language: English
• Subjects: Catalysis; Catalysts; Chemical reactions; Chemistry; Deoxyribonucleic acid; DNA; Enzymes; Esters; Functional groups; Hydrolysis; Imidazole; Natural products; Reaction kinetics; Reagents; Tethering
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c7sc04554a

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.