Protein degraders have a potential to solve some of the challenges in drug discovery, such as drugging undruggable targets, drug resistance and selectivity. The heterobifunctional degraders (proteolysis-targeting chimeras or PROTACs) function to bring the target protein and E3 ubiquitin ligase in close proximity to each other and by forming a ternary complex enable polyubiquitination and degradation of the target protein. Apart from complexity and many unknown variables in the degradation pathway, characterization of a stable ternary complex formation essential for the intended downstream effect is very challenging. Understanding the caveats and limitations of the methods used for measuring binding parameters for ternary complex kinetics is key in identifying molecules with a preferred profile and potentially predicting degradation. With this in mind, we discuss our learnings on how to build a biochemical and biophysical toolbox to assess the mechanism of ternary complex formation using simulation, SPR, and TR-FRET based methods.

Making the right measurement: Biochemical/biophysical tools to dissect ternary complex formation mechanisms

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.