Scientific poster: On-DNA Hit Validation from DNA-Encoded Library Screenings by Focal Molography

This scientific poster, presented at the "13th International Symposium on DNA-Encoded Chemical Libraries" in Boston, MA, USA (Aug 14-15, 2025),  describes a novel hit characterization methodology in drug discovery, for kinetic and affinity assessments after DEL screenings.

Focal molography introduces an innovative solution for the label-free detection and analysis of biomolecular interactions, offering high sensitivity, specificity, and robustness. This technique uses a unique optical diffraction-based sensing approach, where interactions between DEL small molecules and target proteins generate optical signals, providing real-time quantitative data. Each DEL hit is immobilized on a multiplexed sensor chip containing up to 64 individual sensing spots, allowing simultaneous kinetic characterization of hits with minimal protein sample consumption. Respective sensor chips are optimized for on-DNA hit immobilization allowing for simple and robust sensor functionalization.

Our study demonstrates the application of focal molography to streamline the secondary screening phase of DEL campaigns. By utilizing this technology, we performed detailed kinetic measurements, such as on-rates (kon), off-rates (koff), and dissociation constants (KD), of DEL hits in a simple and efficient workflow. Additionally, focal Molography enables researchers to evaluate off-target binding by using complex biological environments, including tissue extracts and cell lysates, further validating the hits’ specificity and potential for therapeutic development