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Issue 7, 2018
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A densely modified M2+-independent DNAzyme that cleaves RNA efficiently with multiple catalytic turnover

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Abstract

Sequence-specific cleavage of RNA targets in the absence of a divalent metal cation (M2+) has been a long-standing goal in bioorganic chemistry. Herein, we report the in vitro selection of novel RNA cleaving DNAzymes that are selected using 8-histaminyl-deoxyadenosine (dAimTP), 5-guanidinoallyl-deoxyuridine (dUgaTP), and 5-aminoallyl-deoxycytidine (dCaaTP) along with dGTP. These modified dNTPs provide key functionalities reminiscent of the active sites of ribonucleases, notably RNase A. Of several such M2+-free DNAymes, DNAzyme 7-38-32 cleaves a 19 nt all-RNA substrate with multiple-turnover, under simulated physiological conditions wherein only 0.5 mM Mg2+ was present, attaining values of kcat of 1.06 min−1 and a KM of 1.37 μM corresponding to a catalytic efficiency of ∼106 M−1 min−1. Therefore, Dz7-38-32 represents a promising candidate towards the development of therapeutically efficient DNAzymes.

Graphical abstract: A densely modified M2+-independent DNAzyme that cleaves RNA efficiently with multiple catalytic turnover

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Publication details

The article was received on 17 Oct 2017, accepted on 04 Jan 2018 and first published on 16 Jan 2018


Article type: Edge Article
DOI: 10.1039/C7SC04491G
Citation: Chem. Sci., 2018,9, 1813-1821
  • Open access: Creative Commons BY license
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    A densely modified M2+-independent DNAzyme that cleaves RNA efficiently with multiple catalytic turnover

    Y. Wang, E. Liu, C. H. Lam and D. M. Perrin, Chem. Sci., 2018, 9, 1813
    DOI: 10.1039/C7SC04491G

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