Investigating new classes of bioorthogonal click-to-release reactions and the development of targeted therapeutic strategies

Project ID: 2531ad1507

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UCL Lead department: Chemistry

Lead Supervisor: James Baker

Project Summary:

Why this research is important: Click Chemistry has had a transformative impact on diverse fields, notably leading to award of the 2022 Nobel prize in Chemistry for its discovery and development. A far less explored but related concept, with similar transformative potential, is ‘Click-to-Release (CtR)’, which involves the two matched partners reacting and leading to a decoupling process. This concept is finding use in applications ranging from drug release in vivo (e.g. from a pro-drug), to controlled ‘turn-on’ of biological pathways and responsive materials. However, a significant hindrance to progress in this area is the limited number of chemical reactions that have been developed to meet the requirements for applicable to CtR, including being rapid, selective, high yielding, biocompatible, and bioorthogonal. We have recently uncovered a potentially powerful new mechanistic class of bioorthogonal CtR reactions. This PhD studentship’s aims include expanding the scope of these click-type reactions by investigating diverse reactive partners (designing, synthesising and tuning their properties), and applying such methodologies to antibody conjugates towards the discovery of new targeted therapeutic strategies. Who you will be working with: You will be working as part of a highly motivated, collaborative research group, investigating at the forefront of chemical biology. Our group culture is a friendly, supportive, encouraging and inquisitive one. There will also be opportunities to collaborate with other groups at UCL and KCL working on cancer therapeutics/diagnostics. What you will be doing: This project will involve organic synthesis, reaction discovery, and bioconjugate construction/analysis. Training and support will be provided in all these aspects. Who we are looking for: We are looking for a highly motivated organic chemist who is keen to work on the interface of organic chemistry with biology/medicine.