PROTAC agents that bind to bacterial toxins as a potentially novel antimicrobial strategy

Project Summary

The goal of this proposal is to establishing non-traditional antibiotic strategies by developing small molecule agents that bind to bacterial toxins and drive their specific degradation by its tagging with ubiquitin. The use of small molecules to drive protein degradation is known as proteolysis targeting chimera (PROTAC). PROTAC agents are heterobifunctional molecules hijacks the ubiquitin proteasome system to specifically and catalytically degrade proteins that cause various diseases. Bacterial pathogens secrete proteins (toxins) that damage the host during active points of infection. For several of these toxins, they are internalized into the host cells, where they can interfere with normal function and be potentially lethal. In this BDSI proposal, the Pires and Im groups will join their expertise to design and assemble PROTAC agents that bind to bacterial toxins as a potentially novel antimicrobial strategy.