Protein Ligand Interactions Using Surface Plasmon Resonance.

Area of Science:

• Biophysics
• Chemical Biology
• Drug Discovery

Background:

• Surface Plasmon Resonance (SPR) is a label-free, real-time biophysical technique.
• SPR is instrumental in characterizing molecular interactions, particularly protein-ligand binding.
• Its application is vital in developing targeted protein degraders.

Purpose of the Study:

• To detail the use of SPR for characterizing small molecule ligands binding to the Thalidomide Binding Domain of mouse Cereblon (mCRBN-TBD).
• To highlight SPR's role in assessing binding kinetics, affinity, and optimizing heterobifunctional ligands for targeted protein degradation.

Main Methods:

• Utilized Surface Plasmon Resonance (SPR) on a Biacore 8K+ instrument.
• Characterized binary interactions between ligands and mCRBN-TBD.
• Analyzed binding kinetics and affinity for ligand triage and optimization.

Main Results:

• Demonstrated SPR's efficacy in quantifying ligand binding to mCRBN-TBD.
• Showcased the ability to rapidly assess binding kinetics and affinity.
• Highlighted SPR's throughput for efficient degrader optimization.

Conclusions:

• SPR is a powerful and indispensable tool for the development and optimization of targeted protein degraders.
• The Biacore 8K+ platform enhances the speed and efficiency of ligand screening.
• SPR facilitates a deeper understanding of molecular interactions critical for drug discovery.