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    Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences

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    wright_et_al_2016.pdf (912.7Kb)
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    Publication date
    2016-12-22
    Author
    Wright, E.P.
    Day, H.A.
    Ibrahim, Ali M.
    Kumar, Jeethendra
    Boswell, L.J.E.
    Huguin, C.
    Stevenson, C.E.M.
    Pors, Klaus
    Keyword
    DNA; Drug discovery; Drug development
    Rights
    © 2016 The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
    Peer-Reviewed
    Yes
    
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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.
    URI
    http://hdl.handle.net/10454/11163
    Version
    Published version
    Citation
    Wright EP, Day HA, Ibrahim AM et al (2016) Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences. Nature Scientific Reports. 6: 39456.
    Link to publisher’s version
    http://dx.doi.org/10.1038/srep39456
    Type
    Article
    Collections
    Life Sciences Publications

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