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

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.

SUBMITTER: Wright EP

PROVIDER: S-EPMC5177923 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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

Wright Elisé P EP Day Henry A HA Ibrahim Ali M AM Kumar Jeethendra J Boswell Leo J E LJ Huguin Camille C Stevenson Clare E M CE Pors Klaus K Waller Zoë A E ZA

Scientific reports 20161222

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 ...[more]

PMID: 28004744

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