Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences
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
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, mitoxantronewas 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.
Circular dichroism, DNA structure, Ligand binding, Biochemistry