Targeting DNA’s Secret Secondary Structures

Zoe Waller (primary)
Pharmaceutical and Biological Chemistry
Lesley Howell (secondary)


It is often assumed that DNA exists only as the iconic Watson-Crick “twisted ladder” double helix; but it can actually adopt many different types of structures. These “alternative” structures may play a role in gene expression [whether genes are switched on or off] and also in the development and progression of genetic diseases such as cancer and diabetes. Targeting these alternative DNA structures could allow for specific therapeutics for disease. This project involves developing new compounds to target i-motif DNA structures for use as tools to learn how DNA structures affect genes and to create leads for pre-clinical development.


1 DNA G-Quadruplex and i-Motif Structure Formation Is Interdependent in Human Cells
JJ King, KL Irving, CW Evans, RV Chikhale, R Becker, CJ Morris, CD Peña Martinez, P Schofield, D Christ, LH Hurley, ZAE Waller, KS Iyer, NM Smith
Journal of the American Chemical Society 142 [49], 2020, 20600-20604

2 Beyond Solvent Exclusion: i-Motif Detecting Capability and an Alternative DNA Light-Switching Mechanism in a Ruthenium II Polypyridyl Complex
P Spence, J Fielden, ZAE Waller
Journal of the American Chemical Society, 2020, 142 [32], 13856-13866

3 Identification of multiple genomic DNA sequences which form i-motif structures at neutral pH
EP Wright, JL Huppert, ZAE Waller
Nucleic acids research, 2017, 45 [6], 2951-2959

4 Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay
Q Sheng, JC Neaverson, T Mahmoud, CEM Stevenson, SE Matthews, ZAE Waller
Organic & biomolecular chemistry, 2017, 15 [27], 5669-5673

5 Identification and characterisation of a G-quadruplex forming sequence in the promoter region of nuclear factor [erythroid-derived 2]-like 2 [Nrf2]
ZAE Waller, LA Howell, CJ MacDonald, MA O’Connell, M Searcey
Biochemical and biophysical research communications, 2014, 447 [1], 128-132

Molecules, cells and industrial biotechnology
Area of Biology
Chemical BiologyStructural Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsChemistryMicroscopy / ElectrophysiologyMolecular Biology