Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1039/c8sc02418a

Type

Journal article

Journal

Chem Sci

Publication Date

21/10/2018

Volume

9

Pages

7681 - 7687