G-Quadruplex DNA (QDNA) motifs have been observed to form in various important regions of the human genome, contributing to cellular processes such as gene expression, DNA replication, and telomere maintenance. The relevance of these processes to cancer cell function and proliferation has drawn recent attention towards QDNA as a therapeutic target. This project contributes to the field by synthesising several heteroleptic platinum(II) complexes for the purpose of stabilising QDNA.A total of twelve novel heteroleptic complexes were synthesised, based on previously reported homoleptic bis-phenanthroline complexes. Of the synthesised complexes, ten incorporated the 4,7-diphenyl-1,10-phenanthroline ligand in combination with either a polyaromatic ligand (PL) or a diamminocyclohexane (DACH) enantiomer. The remaining two complexes incorporated 1,10-phenanthroline in combination with another PL. Interestingly, these bis-phenanthroline complexes were found to be quite labile, thus various methods of microwave-assisted synthesis were investigated.The QDNA binding affinity of the complexes was assessed using a combination of docking simulations, electrospray ionisation mass spectrometry (ESI-MS) binding experiments, and circular dichroism (CD) experiments. All the of the tested complexes exhibited a good binding affinity for QDNA, with a direct correlation observed between complex aromaticity and binding affinity.
Date of Award | 2019 |
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Original language | English |
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- DNA-binding proteins
- DNA-protein interactions
- DNA-ligand interactions
- transition metal complexes
- synthesis
- gene expression
- telomere
Quadruplex stabilising Pt(II) complexes
Jurisinec, A. (Author). 2019
Western Sydney University thesis: Master's thesis