The synthesis of small molecule tools to study biological processes

Begum, Fahmida (2023) The synthesis of small molecule tools to study biological processes. Masters by Research thesis (MSc), Manchester Metropolitan University.

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Abstract

This thesis consists of three separate chapters with individual projects: 1. Chapter 1: Developing a Chemical Biological Approach to Study E3 Ligase Activity: This is the main project of this thesis; this project aims to develop a novel chemical approach to study the formation of PPIs (Protein-Protein Interactions) in cells. The PPI system that is of interest is the ubiquitin proteasome system (UPS), with the aim to develop a set of chemical tools to study the biological activity of E3 ligases that have been recently discovered as potential drug targets. 2. Chapter 2: Understanding the Mechanism of PTC-209, a Potential Protein Translation Inhibitor (completed at the University of Toronto): The project aims are to better understand mechanism of PTC-209, as currently the known mechanism of PTC-209 is not strongly supported. Utilising the aminothiazole central core that is present in PTC-209 as a building block and varying the fragments to help identify what causes the activity seen in literature. 3. Chapter 3: Synthesis of a Lysine Covalent Ibrutinib Derivative (completed at the University of Toronto): This project aims to find an alternative solution to effectively inhibit BTK for treatment of B cell tumours. With the aim to alter ibrutinib’s scaffold to overcome the current ibrutinib design that results in patient relapse and is explained by the mutation of the targeted residue.