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Title: Optimisation of a new class of peptide-based MRI contrast agent
Author: Newton, Sarah Lauren
ISNI:       0000 0004 7230 8872
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2018
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To determine the effect rotational correlation time (rR) has on relaxivity, peptides of different lengths were investigated. Extending the length of the peptide had a negligible impact on folding, stability and inner-sphere water coordination. The relaxivity was found to be the same indicating that TR is not the limiting factor in this class of contrast agent. A peptide was designed with the potential to increase secondary sphere water coordination to the peptide exterior. No change in relaxivity was observed, compared to MB1-2, due secondary sphere H20 being located at too far from the paramagnetic Gd(III). Secondary sphere water coordination was further investigated when a water channel was identified. The channel allows water to come within close proximity of Gd(III), with the potential to increase relaxivity. D-amino acids were introduced in an attempt to block the water channel, but this had little impact. Finally, the biological activity of the peptides in biological systems was investigated. It was found that increased transmetalation occurred when the Gd(III) binding site was located at the Nterminus of the coiled coil. Cell lines were treated with Gd(MB 1-1 )3 at MRI relevant concentrations and cell death occurred when treated with clinically relevant concentrations of the metallo peptide.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry