student profile: Ms Laura Jowett


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Thesis work

Thesis title: Exploring Selective Anion Transport in Novel and Existing Small Molecules

Supervisors: Katrina JOLLIFFE , Philip GALE

Thesis abstract:

Firstly, a novel series of chloride transporters named 'perenosins', based on the natural product prodigiosin, which shows anti-cancer properties, were synthesised. These compounds have a modular synthetic approach and so are easily manipulated to explore a variety of properties essential for anion binding and transport. The protonatable imine allows chloride binding but also a pathway for degradation which could be useful for therapeutic design. The chloride anion binding results showed that protonation was required for chloride binding, and once protonated the perenosins exhibited strong binding affinities. The chloride transport capabilities were assed in a variety of different vesicle based assays, and one of the compounds was found to be comparable to the natural product. It was also found that due to the requirement of protonation for binding and transporting chloride this meant that there was no overall selectivity for chloride alone. Further cell tests gave an insight into the cytotoxicity of the compounds compared to prodigiosin.
Secondly, the transport properties of an existing series of compounds were revisited after some newly developed anion uniport assays showed that earlier transport efficiencies had been vastly underestimated.

Selected publications

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Journals

  • Pankratova, N., Cuartero, M., Jowett, L., Howe, E., Gale, P., Bakker, E., Crespo, G. (2018). Fluorinated tripodal receptors for potentiometric chloride detection in biological fluids. Biosensors and Bioelectronics, 99, 70-76. [More Information]
  • Jowett, L., Howe, E., Soto-Cerrato, V., Van Rossom, W., Perez-Tomas, R., Gale, P. (2017). Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents. Scientific Reports, 7(1), 1-11. [More Information]

2018

  • Pankratova, N., Cuartero, M., Jowett, L., Howe, E., Gale, P., Bakker, E., Crespo, G. (2018). Fluorinated tripodal receptors for potentiometric chloride detection in biological fluids. Biosensors and Bioelectronics, 99, 70-76. [More Information]

2017

  • Jowett, L., Howe, E., Soto-Cerrato, V., Van Rossom, W., Perez-Tomas, R., Gale, P. (2017). Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents. Scientific Reports, 7(1), 1-11. [More Information]

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