Metallo-supramolecular helicates and their ability to bind to higher-order DNA structures

Stock, Hannah Mary Peters (2025). Metallo-supramolecular helicates and their ability to bind to higher-order DNA structures. University of Birmingham. M.Res.

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Abstract

Targeting DNA in order to develop therapeutic agents which treat disease is commonplace as many disorders arise from the expression of DNA, where the amplification, and expression as RNA or proteins, of the DNA code has led to the disease manifestation. However, many DNA-binding agents are non-specific and bind non-selectively to DNA, affecting numerous genes and consequently, many cellular processes.

Despite this, metallo-supramolecular compounds have shown the ability to overcome the selectivity issues of other DNA-binding agents, through structure specific targeting of DNA. A metallo-supramolecular helicate, previously developed by the Hannon group, demonstrated the ability to selectively target higher-order DNA structures, such as DNA three-way junctions (3WJs), four-way junctions (4WJs) through structure specific binding mechanisms. Here a significantly longer metallo-supramolecular helicate was synthesised in order to investigate how length impacted the ability of a helicate to bind to higher-order DNA structures. A number of in vitro and in silica experiments were conducted, which demonstrated that the novel helicate bound to the central cavity of both 3WJs and 4WJs in a similar way to previously developed helicates, and furthermore, that the different enantiomers of this novel helicate showed differing binding activity.

Overall, the research presented in this thesis adds a new triple-stranded helicate to the current, known portfolio and also presents a metallo-supramolecular helicate that has demonstrated a strong ability to bind to higher-order DNA, suggesting its potential application to therapeutics.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):