Protein Ligand Interactions Using Surface Plasmon Resonance.

Surface Plasmon Resonance (SPR) is a powerful biophysical method for characterizing small molecule binding to proteins. Owing to its ability to characterize binary inteactions between warheads and E3 ligases or substrates, SPR is a useful tool for the development of targeted protein degraders. SPR is also an effective method for optimizing linkers and characterizing ternary complex interactions that are mediated by heterobifunctional ligands (Roy et al. ACS Chem Biol 14:361-368, 2019). Recent advances in the throughput of modern instruments have improved the ability of SPR to rapidly triage ligands based on binding kinetics and affinity, making this technique invaluable for driving degrader optimization. This chapter describes the characterization of ligands binding to the Thalidomide Binding Domain of mouse Cereblon (mCRBN-TBD) using the Biacore 8K+.