Exploring BacPROTACs as a New Paradigm for Antibacterial Discovery

Erick Strauss of Stellenbosch University in South Africa, in collaboration with co-investigators Andrew Whitelaw also of Stellenbosch University, Adrienne Edkins of Rhodes University in South Africa and Miquel Duran-Frigola of Ersilia Open Source Initiative in Spain will pursue the discovery of new Gram-negative antibacterials through the development of bacterial proteolysis targeting chimeras (BacPROTACs) - bifunctional molecules designed to engage high value protein targets and an endogenous intracellular protease in the pathogen to induce proteolytic degradation. In this manner, BacPROTACs use targeted protein degradation (TPD) as a highly innovative strategy to achieve an antibacterial outcome. The team proposes to use this approach to establish a BacPROTAC development workflow that can be applied for the identification of new chemical leads for any validated drug target or resistance-inducing factor that can be shown to be degraded by the pathogen’s endogenous protease, and for which a target-engaging ligand (TEL) can be identified.

This grant is funded by The Wellcome Trust.