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Fluorogenic thiazole orange TOTFO probes stabilise parallel DNA triplexes at pH 7 and above

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Abstract

The instability of DNA triplexes particularly at neutral pH and above severely limits their applications. Here, we demonstrate that the introduction of a thiazole orange (TO) intercalator onto a thymine nucleobase in triplex forming oligonucleotides (TFOs) resolves this problem. The stabilising effects are additive; multiple TO units produce nanomolar duplex binding and triplex stability can surpass that of the underlying duplex. In one example, a TFO containing three TO units increased the triplex melting temperature at pH 7 by a remarkable 50 °C relative to the unmodified triplex. Notably, TO intercalation promotes TFO binding to target sequences other than pure polypurine tracts by the use of 5-(1-propynyl)cytosine (pC) against C:G inversions. By overcoming the instability of triplexes across a broad range of pH and sequence contexts, these very simple ‘TOTFO’ probes could expand triplex applications into many areas including diagnostics and cell imaging.

Graphical abstract: Fluorogenic thiazole orange TOTFO probes stabilise parallel DNA triplexes at pH 7 and above

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Publication details

The article was received on 01 Jun 2018, accepted on 30 Jul 2018 and first published on 01 Aug 2018


Article type: Edge Article
DOI: 10.1039/C8SC02418A
Citation: Chem. Sci., 2018, Advance Article
  • Open access: Creative Commons BY-NC license
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    Fluorogenic thiazole orange TOTFO probes stabilise parallel DNA triplexes at pH 7 and above

    S. Walsh, A. H. El-Sagheer and T. Brown, Chem. Sci., 2018, Advance Article , DOI: 10.1039/C8SC02418A

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