Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media
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 t...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-11-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/23/11/2941 |
| _version_ | 1818268912547004416 |
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| author | Melissa Meng Boris Schmidtgall Christian Ducho |
| author_facet | Melissa Meng Boris Schmidtgall Christian Ducho |
| author_sort | Melissa Meng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T20:46:02Z |
| format | Article |
| id | doaj.art-78ecaa1c6e084dd4b5d68101b8b53dfc |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T20:46:02Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-78ecaa1c6e084dd4b5d68101b8b53dfc2022-12-22T00:12:34ZengMDPI AGMolecules1420-30492018-11-012311294110.3390/molecules23112941molecules23112941Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological MediaMelissa Meng0Boris Schmidtgall1Christian Ducho2Saarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, GermanySaarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, GermanySaarland University, Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Campus C2 3, 66123 Saarbrücken, GermanyDeficient 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.https://www.mdpi.com/1420-3049/23/11/2941DNAoligonucleotidesbackbone modificationsnucleasesbiological media |
| spellingShingle | Melissa Meng Boris Schmidtgall Christian Ducho Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media Molecules DNA oligonucleotides backbone modifications nucleases biological media |
| title | Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media |
| title_full | Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media |
| title_fullStr | Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media |
| title_full_unstemmed | Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media |
| title_short | Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media |
| title_sort | enhanced stability of dna oligonucleotides with partially zwitterionic backbone structures in biological media |
| topic | DNA oligonucleotides backbone modifications nucleases biological media |
| url | https://www.mdpi.com/1420-3049/23/11/2941 |
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