Glucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly expanding class of therapeutics for the treatment of various metabolic diseases. Characterization of their binding kinetics is essential for understanding mechanism of action, optimizing receptor engagement, and differentiating candidate molecules early in development. 

When analyzing peptides using label-free biosensors, the complexity involved in assay development requires a high level of expertise and places hurdles in accessing high-quality data. Optimal assay methods may be challenging and time-consuming to develop. Key challenges include non-specific binding, maintaining the peptide’s stability and activity, the difficulty in detecting small molecules/peptides, and challenges with site-specific immobilization.

In this application note, we demonstrate how Nicoya’s Digital Surface Plasmon Resonance (SPR) instruments offer a powerful platform for measuring real-time binding interactions of peptides. This application note outlines impactful experimental strategies for measuring kinetics and binding affinity of the GLP-1R agonist semaglutide with Digital SPR. Various assay formats and capture surfaces will be discussed, including best practices for assay optimization and data analysis.