High-Throughput Binder Confirmation Using Affinity Selection Mass Spectrometry.

Affinity selection mass spectrometry (AS-MS) was recently applied to a new high-throughput binder confirmation (HTBC) platform. The HTBC-AS-MS platform can assess target engagement for hundreds of chemical series per target and is used at GSK to prioritize synthesis decisions for follow-up organic synthesis of DNA-encoded library technology (ELT) hits.

DNA-Encoded Library Hit Confirmation: Bridging the Gap Between On-DNA and Off-DNA Chemistry.

DNA-encoded library (DEL) technology is a powerful platform for hit identification in academia and the pharmaceutical industry. When conducting off-DNA resynthesis hit confirmation after affinity selection, PCR/sequencing, and data analysis, one typically assumes a "one-to-one" relationship between the DNA tag and the chemical structure of the attached small-molecule it encodes. Because library synthesis often yields a mixture, this approximation increases the risk of overlooking positive discoveries and valuable information.