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Affinity-guided chemical probes for the study of protein interactions

Beard, Hester Annie (2018) Affinity-guided chemical probes for the study of protein interactions. PhD thesis, University of Leeds.

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Beard_HA_Chemistry_PhD_2018.pdf - Final eThesis - complete (pdf)
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Abstract

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.

Item Type: Thesis (PhD)
Keywords: Chemical labelling Traceless affinity labelling Photoaffinity probes Photocrosslinking
Academic Units: The University of Leeds > Faculty of Maths and Physical Sciences (Leeds) > School of Chemistry (Leeds)
Depositing User: Ms Hester Beard
Date Deposited: 19 Jun 2018 09:34
Last Modified: 19 Jun 2018 09:34
URI: http://etheses.whiterose.ac.uk/id/eprint/20637

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