DNAmoreDB - A Database of Deoxyribozymes

Published on 2018 in Chem.Sci. volume 9.

DOI:10.1039/C7SC04491G

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.



DNAzymes linked to this article:

Name Isolated sequence Length Reaction
Dz7-38-39 TTACAGTGGTATCGATTGGGACGTGTGGAGCGTCAGGATGGTATA      45 RNA cleavage
Dz7-38-83 TTACAGTGGTATCGATTGGGACGTGTGTAGCGTCAGGATGGGATCA      46 RNA cleavage
Dz7-38-32 TTACAGTGGTATCGATTGGGACGTGTGGAGCGTCAGGATGGTACA      45 RNA cleavage
7-10 TTACAGTGGTAGCGGTTGGCACGTGTGCAGCGTAAGTGGGCG      42 RNA cleavage
7-38 TTACAGTGGTAGCGGTTGGCATGTGTGCAGCGTAGGTGGGCG      42 RNA cleavage
7-44 TTACAGTGGTAGCGGTGGCATGTGTACAGCGTTAGTGAGTG      41 RNA cleavage
7-50 TTATAGTGGTAGCGGTTGGCATGTGTGTGGCGTGAGTTAGTG      42 RNA cleavage
7-55 TTACAGTGGTAGCGGTTGGCATGTGTGGAGCGTAAGTGAGCG      42 RNA cleavage
7-57 TTACAGTGGTAGCGGTTGGCATGTGTGCAGCGTAAGTGGGCG      42 RNA cleavage
7-60 TTACAGTCGTAGCGGTGGCATGCGTGCAGAGTAAGTGGGCG      41 RNA cleavage
7-45 AAGCAGCGCATGTGATGGCACGCGTAGTGGCTGGGTAGCT      40 RNA cleavage
Dz7-38-90 TTACAGTGGTATCGATTGGGACGTGTGGAGCGTCAGGATGGGATCA      46 RNA cleavage
Dz7-45-10 AAGCAGCGGATGTGGTGTGACGCGGAGTCCCGAGTAGGGCTT      42 RNA cleavage
Dz7-45-22 AAGCAGCGGATGTGGTGTGACGCGGAGTCCCGGGTAGGGCTT      42 RNA cleavage
Dz7-45-28 AAGCAGCGGACGGATGGATGCGGAGTGCCTGAGTCAGGCCTT      42 RNA cleavage
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