Novel bifunctional chemistries for exploration of targeted protein degradation mechanisms

Small molecules that can selectively target proteins for degradation, as opposed to simply inhibiting their function, are proving to be invaluable research tools for life scientists to understand a wide range of cellular function and provide the potential for a new generation of breakthrough therapeutics. Proteolysis Targeting Chimeras (PROTACs) are two-headed molecules that achieve this goal by binding with one head to a target protein and with another head to an E3 ubiquitin ligase and inducing the proximity and ubiquitination/degradation of the target protein.

Such approaches to date have been largely utilised in the context of understanding and treating cancer however there is much broader potential to develop these approaches as tools to understand biological pathways in many different contexts.

This project will focus on developing chemical library synthesis and testing approaches to deliver tools that selectively degrade protein(s) implicated in a wide range of neuronal function. This will enable exploration of novel concepts that have potential to transform our understanding of how the UPS can be harnessed and purposefully directed within the central nervous system. To achieve this goal methods and reagents will be developed that will find utility amongst the many life science research groups and organisations currently pursuing proximity inducing modalities, including but not limited to targeted protein degradation.