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

米托蒽醌及其类似物结合并稳定 i-Motif 形成 DNA 序列

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作者:Elisé P Wright, Henry A Day, Ali M Ibrahim, Jeethendra Kumar, Leo J E Boswell, Camille Huguin, Clare E M Stevenson, Klaus Pors, Zoë A E Waller

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.

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