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

This poster was presented at the "13th International Symposium on DNA-Encoded Chemical Libraries" in Boston, MA, USA (Aug 14-15, 2025). It describes a hit characterization method for kinetic and affinity assessment after DEL screenings.

Focal molography detects and analyzes biomolecular interactions label-free, with high sensitivity and specificity. 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 with up to 64 individual sensing spots. All hits are characterized kinetically at once, with minimal protein 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 speed up the secondary screening phase of DEL campaigns. With this technology, we measured on-rates (kon), off-rates (koff), and dissociation constants (KD), of DEL hits in a simple and efficient workflow. Focal molography also lets researchers evaluate off-target binding in complex biological media, including tissue extracts and cell lysates. That further validates the hits’ specificity and therapeutic potential