School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
Sci Rep. 2016 Dec 22;6:39456. doi: 10.1038/srep39456.
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.
有数百种配体可以与 G-四链体 DNA 相互作用，但很少有可以靶向 i- 发夹结构的配体。为了更好地理解这些结构之间的动态关系，以及它们如何受到小分子配体干预的影响，我们需要更多的 i- 发夹结构结合化合物。本文描述了米托蒽醌如何结合、诱导折叠并稳定 i- 发夹结构形成的 DNA 序列，即使在生理 pH 值下也是如此。此外，还发现米托蒽醌优先结合 i- 发夹结构形成的序列，而不是双链 DNA。我们还描述了米托蒽醌类似物的稳定特性。这为一类具有潜在用途的新型配体提供了可能，可用于研究 i- 发夹结构形成的 DNA 序列的结构和功能。
