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Molecules 2018, 23(11), 2941; https://doi.org/10.3390/molecules23112941

Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media

1
Saarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, Germany
2
University of Paderborn, Department of Chemistry, Warburger Str. 100, 33098 Paderborn, Germany
In memory of Professor Joachim Engels (1944–2018).
*
Author to whom correspondence should be addressed.
Received: 29 October 2018 / Revised: 6 November 2018 / Accepted: 8 November 2018 / Published: 10 November 2018
(This article belongs to the Special Issue Bioactive Nucleosides and Nucleotides)
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Abstract

Deficient stability towards nuclease-mediated degradation is one of the most relevant tasks in the development of oligonucleotide-derived biomedical agents. This hurdle can be overcome through modifications to the native oligonucleotide backbone structure, with the goal of simultaneously retaining the unique hybridization properties of nucleic acids. The nucleosyl amino acid (NAA)-modification is a recently introduced artificial cationic backbone linkage. Partially zwitterionic NAA-modified oligonucleotides had previously shown hybridization with DNA strands with retained base-pairing fidelity. In this study, we report the significantly enhanced stability of NAA-modified oligonucleotides towards 3′- and 5′-exonuclease-mediated degradation as well as in complex biological media such as human plasma and whole cell lysate. This demonstrates the potential versatility of the NAA-motif as a backbone modification for the development of biomedically active oligonucleotide analogues. View Full-Text
Keywords: DNA; oligonucleotides; backbone modifications; nucleases; biological media DNA; oligonucleotides; backbone modifications; nucleases; biological media
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Meng, M.; Schmidtgall, B.; Ducho, C. Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media. Molecules 2018, 23, 2941.

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