Mitoxantrone and analogues bind and stabilize i-motif forming DNA sequences

Wright, Elisé P., Day, Henry A., Ibrahim, Ali M., Kumar, Jeethendra, Boswell, Leo J. E., Huguin, Camille, Stevenson, Clare E. M., Pors, Klaus and Waller, Zoë A. E. (2016) Mitoxantrone and analogues bind and stabilize i-motif forming DNA sequences. Scientific Reports, 6. ISSN 2045-2322

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Abstract

There are hundreds of ligands which can interact with G-quadruplex DNA, yet very few which target i-motif. To appreciate an understanding between the dynamics between these structures and how they can be affected by intervention with small molecule ligands, more i-motif binding compounds are required. Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. Additionally, mitoxantrone was found to bind i-motif forming sequences preferentially over double helical DNA. We also describe the stabilisation properties of analogues of mitoxantrone. This offers a new family of ligands with potential for use in experiments into the structure and function of i-motif forming DNA sequences.

Item Type: Article
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Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017)
Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
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Depositing User: Pure Connector
Date Deposited: 05 Jan 2017 00:02
Last Modified: 28 Jul 2023 02:44
URI: https://ueaeprints.uea.ac.uk/id/eprint/61917
DOI: 10.1038/srep39456

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