Targeted Protein Degradation through Site-Specific Recruitment of Ubiquitin Ligase

University of Pittsburgh researchers have developed a novel technology that enhances the potential of PROTACs (PROteolysis TArgeting Chimeras) by enabling targeted protein degradation through site-specific recruitment of ubiquitin ligase. This technology allows for the evaluation of protein degradability even in the absence of a small molecule ligand, offering an advanced novel strategy in drug discovery and precision medicine.

Description

PROTACs are a class of small molecule drugs designed to selectively degrade disease-causing proteins. They consist of two key components: a ligand that binds to the target protein and a ligand that recruits an E3 ubiquitin ligase, which tags the protein for degradation by the proteasome. This technology overcomes the limitation of requiring a potent small molecule ligand by allowing site-specific placement of E3 ligase ligands on the protein surface, enabling the exploration of new binding sites for potential ligands.

Applications

• Drug discovery
• Precision medicine
• Oncology research
• Biotechnology services

Advantages

This technology provides a unique therapeutic strategy to the pharmaceutical and biotech industries by enabling the investigation of PROTAC development feasibility for specific protein targets before discovering a small molecule ligand. It guides the development of optimal PROTACs by identifying the best sites for E3 ligase recruitment, potentially transforming the approach to targeting “undruggable” proteins and offering new therapeutic avenues.

Invention Readiness

The technology is currently at the prototype stage. A prototype has been developed that demonstrates the ability to site-specifically place E3 ligase ligands on the surface of target proteins. Initial protein degradation assays have been conducted, showing successful degradation of target proteins in the absence of a small molecule ligand. Experiments have identified multiple putative binding sites on the protein surface for E3 ligase recruitment, allowing for the exploration of new small molecule ligands.

IP Status

https://patents.google.com/patent/WO2024249187A1