Abstract
A novel concept to improve the catalytic functions of nucleic acids (DNAzymes) is introduced. The method involves the conjugation of a DNA recognition sequence (aptamer) to the catalytic DNAzyme, yielding a hybrid structure termed "nucleoapzyme". Concentrating the substrate within the "nucleoapzyme" leads to enhanced catalytic activity, displaying saturation kinetics. Different conjugation modes of the aptamer/DNAzyme units and the availability of different aptamer sequences for a substrate provide diverse means to design improved catalysts. This is exemplified with (i) The H2O2-mediated oxidation of dopamine to aminochrome using a series of hemin/G-quadruplex-dopamine aptamer nucleoapzymes. All nucleoapzymes reveal enhanced catalytic activities as compared to the separated DNAzyme/aptamer units, and the most active nucleoapzyme reveals a 20-fold enhanced activity. Molecular dynamics simulations provide rational assessment of the activity of the various nucleoapzymes. The hemin/G-quadruplex-aptamer nucleoapzyme also stimulates the chiroselective oxidation of l- vs d-DOPA by H2O2. (ii) The H2O2-mediated oxidation of N-hydroxy-l-arginine to l-citrulline by a series of hemin/G-quadruplex-arginine aptamer conjugated nucleoapzymes.
Original language | English |
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Pages (from-to) | 164-172 |
Number of pages | 9 |
Journal | Journal of the American Chemical Society |
Volume | 138 |
Issue number | 1 |
DOIs | |
State | Published - 13 Jan 2016 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2015 American Chemical Society.