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Title: Affinity-guided chemical probes for the study of protein interactions
Author: Beard, Hester Annie
ISNI:       0000 0004 7225 7403
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2018
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Chemical methods that allow for the targeted labelling of a specific protein within a complex biological environment can enable valuable information regarding the structure and function of proteins to be gained. This thesis explores two different projects where affinity-guided chemical probes were used to study the interactions of proteins, both with small molecules (Chapter 2) and interacting protein partners (Chapter 3). Firstly, chemical labelling methods based on a recognition unit for the protein of interest are reviewed in Chapter 1. Then, Chapter 2 describes how a combination of chemical tools (including photoaffinity, biotinylated and fluorescent probes) were used to study the interaction of a small molecule inducer of human glioblastoma cell death and its relevant target. This work resulted in the identification of HSPD1 as a potential therapeutic target for the treatment of glioblastoma. Chapter 3 details the development of a method for traceless labelling of B-cell lymphoma 2 (BCL-2) family proteins, using a ruthenium-bipyridyl modified peptide. Myeloid cell leukaemia 1 (MCL-1) was rapidly and selectively labelled with fluorescent and biotinylated tags, in vitro, facilitated by the interaction with a peptide mimicking a binding partner. Overall, this thesis demonstrates how affinity-guided labelling of proteins can be used for understanding molecular mechanisms of disease and mapping protein interactomes.
Supervisor: Bon, Robin Stefan ; Wilson, Andrew John Sponsor: EPSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available