Challenges and Opportunities in DNA Encoded Library Screens

In our lab we have been developing techniques that attempt to capture or amplify signals in pooled compound mixtures for several years. DNA encoded libraries (DELs) are the most widely used pooled mixtures in early drug discovery. DELs are massive collections of small molecules, where each individual molecule is covalently linked to a unique DNA strand that can serve as an identification tag by sequencing. The industry standard for selecting DELs is affinity enrichment, which inherently can only search for direct binding. We outline here two of the ways that we are attempting to extend the potential of DEL screens into new areas.