Rationalisation of a mechanism for sensing single point variants in target DNA using anthracene-tagged base discriminating probes

Jean-Louis H. A. Duprey, Dario M. Bassani, Eva I. Hyde, Gediminas Jonusauskas, Christian Ludwig, Alison Rodger, Neil Spencer, Joseph S. Vyle, John Wilkie, Zheng-Yun Zhao, James H. R. Tucker

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Abstract

The labelling of DNA oligonucleotides with signalling groups that give a unique response to duplex formation depending on the target sequence is a highly effective strategy in the design of DNA-based hybridisation sensors. A key challenge in the design of these so-called base discriminating probes (BDPs) is to understand how the local environment of the signalling group affects the sensing response. The work herein describes a comprehensive study involving a variety of photophysical techniques, NMR studies and molecular dynamics simulations, on anthracene-tagged oligonucleotide probes that can sense single base changes (point variants) in target DNA strands. A detailed analysis of the fluorescence sensing mechanism is provided, with a particular focus on rationalising the high dependence of this process on not only the linker stereochemistry but also the site of nucleobase variation within the target strand. The work highlights the various factors and techniques used to respectively underpin and rationalise the BDP approach to point variant sensing, which relies on different responses to duplex formation rather than just different duplex binding strengths.
Original languageEnglish
Pages (from-to) 6576-6585
Number of pages10
JournalOrganic & biomolecular chemistry
Volume16
Issue number35
Early online date15 Aug 2018
DOIs
Publication statusPublished - 2018

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anthracene
deoxyribonucleic acid
oligonucleotides
strands
probes
DNA
Stereochemistry
Oligonucleotide Probes
stereochemistry
Molecular Dynamics Simulation
Oligonucleotides
Labeling
marking
Molecular dynamics
Fluorescence
Nuclear magnetic resonance
molecular dynamics
fluorescence
nuclear magnetic resonance
sensors

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Duprey, Jean-Louis H. A. ; Bassani, Dario M. ; Hyde, Eva I. ; Jonusauskas, Gediminas ; Ludwig, Christian ; Rodger, Alison ; Spencer, Neil ; Vyle, Joseph S. ; Wilkie, John ; Zhao, Zheng-Yun ; Tucker, James H. R. / Rationalisation of a mechanism for sensing single point variants in target DNA using anthracene-tagged base discriminating probes. In: Organic & biomolecular chemistry. 2018 ; Vol. 16, No. 35. pp. 6576-6585.
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Duprey, J-LHA, Bassani, DM, Hyde, EI, Jonusauskas, G, Ludwig, C, Rodger, A, Spencer, N, Vyle, JS, Wilkie, J, Zhao, Z-Y & Tucker, JHR 2018, 'Rationalisation of a mechanism for sensing single point variants in target DNA using anthracene-tagged base discriminating probes', Organic & biomolecular chemistry, vol. 16, no. 35, pp. 6576-6585. https://doi.org/10.1039/C8OB01710G, https://doi.org/10.1039/c8ob01710g

Rationalisation of a mechanism for sensing single point variants in target DNA using anthracene-tagged base discriminating probes. / Duprey, Jean-Louis H. A.; Bassani, Dario M.; Hyde, Eva I.; Jonusauskas, Gediminas; Ludwig, Christian; Rodger, Alison; Spencer, Neil; Vyle, Joseph S.; Wilkie, John; Zhao, Zheng-Yun; Tucker, James H. R.

In: Organic & biomolecular chemistry, Vol. 16, No. 35, 2018, p. 6576-6585.

Research output: Contribution to journalArticle

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AU - Duprey, Jean-Louis H. A.

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AU - Ludwig, Christian

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AU - Spencer, Neil

AU - Vyle, Joseph S.

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