title: 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.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Elisé P
authors.initials: EP
authors.lastname: Wright
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Henry A
authors.initials: HA
authors.lastname: Day
authors.affiliation: Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Ibrahim
authors.affiliation: Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Jeethendra
authors.initials: J
authors.lastname: Kumar
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Leo J E
authors.initials: LJ
authors.lastname: Boswell
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Camille
authors.initials: C
authors.lastname: Huguin
authors.affiliation: Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.
authors.forename: Clare E M
authors.initials: CE
authors.lastname: Stevenson
authors.affiliation: Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pors
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.|Centre for Molecular and Structural Biochemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: Zoë A E
authors.initials: ZA
authors.lastname: Waller
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008942:Mitoxantrone / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D009841:Oligonucleotides; D020349:Surface Plasmon Resonance; D016615:Telomere / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
chemical_list: D008024:Ligands; D009841:Oligonucleotides; D004247:DNA; D008942:Mitoxantrone