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.

Details

Title
Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media
Author
Meng, Melissa 1 ; Schmidtgall, Boris 2 ; Ducho, Christian 2   VIAFID ORCID Logo 

1  Saarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, Germany 
2  Saarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, Germany; University of Paderborn, Department of Chemistry, Warburger Str. 100, 33098 Paderborn, Germany 
First page
2941
Publication year
2018
Publication date
2018
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.3390/molecules23112941
ProQuest document ID
2582846045
Copyright
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.