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Title: Multivalent scaffolds for use as protein surface mimetics
Author: Hewitt, Sarah Helen
ISNI:       0000 0004 6421 1261
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2017
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The development of ligands for protein surfaces to inhibit protein-protein interactions (PPI)s is challenging, as protein surfaces often lack the clefts and pockets associated with traditionally druggable targets like enzyme active sites. One way in which protein surfaces can be targeted is by the use of protein surface mimetics, whereby a multivalent scaffold is functionalised with many binding groups on its periphery in order to achieve high affinity protein recognition. One such scaffold is a ruthenium(II) tris (bipyridine)s (Ru(II)(bpy)3). The work in this thesis aimed to further develop these Ru(II)(bpy)3 protein surface mimetics; gaining information as to how they interact with proteins, looking at new ways of achieving high affinity protein surface recognition and the development of new applications for these molecules. In Chapter 2 an indepth study of the binding of two Ru(II)(bpy)3 complexes to a model protein, cytochrome c, is presented, looking at the thermodynamic and electrostatic contributions to binding as well as using protein NMR to elucidate the binding site. In Chapter 3 the development of dynamic combinatorial chemistry (DCC) scaffolds based on Ru(II)(bpy)3 complexes and tetraphenyl porphyrins was explored as a potential avenue for new receptor design, enabling the development of biologically compatible DCC systems, prime for protein ligand discovery. Chapter 4 presents another avenue for using the Ru(II)(bpy)3 complexes; using an array approach to discriminate between different protein.
Supervisor: Wilson, Andrew Sponsor: EPSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available