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DOI: 10.1055/sos-SD-241-00195

Georgiev, T.; Cazzamalli, S.; Neri, D.; Bassi, G.Science of Synthesis: DNA Encoded Librariesearly view.

General Introduction

DNA-encoded chemical libraries (DELs) are being increasingly used for de novo discovery and for the optimization of small organic ligands to protein targets of pharmaceutical and biological interest.[‌1‌‌7‌] DELs are typically synthesized either in single- or double-stranded DNA format (ssDELs or dsDELs),[‌1‌‌7‌] with the latter benefitting from enhanced stability due to formation of oligonucleotide heteroduplexes. Both DEL formats are compatible with conventional screening methodologies such as affinity capture[‌8‌,‌9‌] and on-resin selections[‌10‌] (see Section 4.1), and on-cell selections[‌11‌,‌12‌] (see Section 4.3). Our group has previously assessed the impact of the DNA format on selection performance by comparative screening methodologies. In our experiments, ssDELs and dsDELs display comparable performance in affinity-capture selections against model protein targets.[‌13‌]

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