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Review

Molecular Features and Metal Ions That Influence 10-23 DNAzyme Activity

1
Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225 Duesseldorf, Germany
2
Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52428 Jülich, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Michael Smietana, Stellios Arseniyadis and Sabine Müller
Molecules 2020, 25(13), 3100; https://doi.org/10.3390/molecules25133100
Received: 31 May 2020 / Revised: 25 June 2020 / Accepted: 3 July 2020 / Published: 7 July 2020
(This article belongs to the Special Issue Advances in Catalytic DNA)
Deoxyribozymes (DNAzymes) with RNA hydrolysis activity have a tremendous potential as gene suppression agents for therapeutic applications. The most extensively studied representative is the 10-23 DNAzyme consisting of a catalytic loop and two substrate binding arms that can be designed to bind and cleave the RNA sequence of interest. The RNA substrate is cleaved between central purine and pyrimidine nucleotides. The activity of this DNAzyme in vitro is considerably higher than in vivo, which was suggested to be related to its divalent cation dependency. Understanding the mechanism of DNAzyme catalysis is hindered by the absence of structural information. Numerous biological studies, however, provide comprehensive insights into the role of particular deoxynucleotides and functional groups in DNAzymes. Here we provide an overview of the thermodynamic properties, the impact of nucleobase modifications within the catalytic loop, and the role of different metal ions in catalysis. We point out features that will be helpful in developing novel strategies for structure determination and to understand the mechanism of the 10-23 DNAzyme. Consideration of these features will enable to develop improved strategies for structure determination and to understand the mechanism of the 10-23 DNAzyme. These insights provide the basis for improving activity in cells and pave the way for developing DNAzyme applications. View Full-Text
Keywords: catalysis; deoxyribozymes (DNAzymes); gene silencing; metal ion cofactors; RNA hydrolysis catalysis; deoxyribozymes (DNAzymes); gene silencing; metal ion cofactors; RNA hydrolysis
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MDPI and ACS Style

Rosenbach, H.; Victor, J.; Etzkorn, M.; Steger, G.; Riesner, D.; Span, I. Molecular Features and Metal Ions That Influence 10-23 DNAzyme Activity. Molecules 2020, 25, 3100. https://doi.org/10.3390/molecules25133100

AMA Style

Rosenbach H, Victor J, Etzkorn M, Steger G, Riesner D, Span I. Molecular Features and Metal Ions That Influence 10-23 DNAzyme Activity. Molecules. 2020; 25(13):3100. https://doi.org/10.3390/molecules25133100

Chicago/Turabian Style

Rosenbach, Hannah; Victor, Julian; Etzkorn, Manuel; Steger, Gerhard; Riesner, Detlev; Span, Ingrid. 2020. "Molecular Features and Metal Ions That Influence 10-23 DNAzyme Activity" Molecules 25, no. 13: 3100. https://doi.org/10.3390/molecules25133100

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