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Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility

Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility
Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility
DNA strands containing a triazole linkage flanked on its 3?-side by an aminoethylphenoxazine nucleobase analogue (G-clamp) have been prepared by solid-phase synthesis followed by CuAAC-mediated click oligonucleotide ligation. The stability of the doubly modified DNA duplexes and DNA–RNA hybrids is greatly increased, whereas a single base pair mismatch located at or adjacent to the modifications is strongly destabilising, making triazole G-clamp a potent mismatch/point mutation sensor. A DNA strand containing this unnatural combination was successfully amplified by PCR to produce unmodified copies of the original template, with deoxyguanosine inserted opposite to the G-clamp-triazole nucleotide analogue. This study shows for the first time that a polymerase enzyme can read through a combined backbone/nucleobase modification surprisingly well. These favourable properties suggest new applications for oligonucleotides containing the G-clamp triazole modification in biotechnology, nanotechnology, diagnostics and therapeutics.
1478-6524
253-259
El-Sagheer, Afaf H.
05b8295a-64ad-4fdf-ad57-c34934a46c04
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
El-Sagheer, Afaf H.
05b8295a-64ad-4fdf-ad57-c34934a46c04
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89

El-Sagheer, Afaf H. and Brown, Tom (2013) Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility. Chemical Science, 5 (1), 253-259. (doi:10.1039/C3SC51753E).

Record type: Article

Abstract

DNA strands containing a triazole linkage flanked on its 3?-side by an aminoethylphenoxazine nucleobase analogue (G-clamp) have been prepared by solid-phase synthesis followed by CuAAC-mediated click oligonucleotide ligation. The stability of the doubly modified DNA duplexes and DNA–RNA hybrids is greatly increased, whereas a single base pair mismatch located at or adjacent to the modifications is strongly destabilising, making triazole G-clamp a potent mismatch/point mutation sensor. A DNA strand containing this unnatural combination was successfully amplified by PCR to produce unmodified copies of the original template, with deoxyguanosine inserted opposite to the G-clamp-triazole nucleotide analogue. This study shows for the first time that a polymerase enzyme can read through a combined backbone/nucleobase modification surprisingly well. These favourable properties suggest new applications for oligonucleotides containing the G-clamp triazole modification in biotechnology, nanotechnology, diagnostics and therapeutics.

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Published date: 17 October 2013
Additional Information: This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Organisations: Chemistry

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Local EPrints ID: 369278
URI: http://eprints.soton.ac.uk/id/eprint/369278
ISSN: 1478-6524
PURE UUID: 64c9d75b-a035-4664-a3c7-b2d975650c5c

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Date deposited: 23 Sep 2014 10:32
Last modified: 15 Jul 2019 21:43

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Contributors

Author: Afaf H. El-Sagheer
Author: Tom Brown

University divisions

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