Andreas Brunschweiger
Bioorg. Med. Chem., 2021, 116582
https://doi.org/10.1016/j.bmc.2021.116582

Abstract

At first glance, the idea of providing 500 Da drug-like compounds with a molecular identifier that is about 100 times larger and a biomacromolecule takes some getting used to. However, over the past decade, and especially in recent years, DNA-encoded libraries, or DELs, have gained increasing attention from both academic and industrial researchers as a generic small molecule screening technology for a wide range of biological targets. There are several reasons for massively increased research activities in this field. These are ranging from (a) purely technical underpinnings, namely the ready availability of synthetic DNA oligonucleotides, affordable sequencing technology, and computational power to analyze massively large data sets; (b) breakthrough research by a few pioneers that have demonstrated the proof of concept; (c) the promise of the technology, namely harnessing the data storage capability of DNA for efficiently handling and screening vast chemical space on biological targets by a conceptually simple selection assay; to (d) relevance, given the lack of drug development entry points for a large number of disease-relevant biological targets.