3.2.1.1 Encoding Using Double-Stranded DNA: A Headpiece-Based DNA Ligation Strategy

Abstract

DNA-encoded chemical libraries (DELs) provide a powerful high-throughput screening platform that is used in both academia and industry. High-quality DELs lay the foundation for reliable DEL selection outcomes, and most pharmaceutical companies would prefer double-stranded DELs (dsDELs) because of their superior stability. Here, we summarize the experimental details for encoding a dsDEL, including the overall encoding strategy, synthetic chemistry of building-block addition, ligation strategies of code elongation, and quality control of the resulting libraries, exemplified with a 320-million-membered benzimidazole dsDEL from GlaxoSmithKline (GSK). We also briefly review the successful selection cases involving the presented libraries to highlight the great potential of dsDELs in drug discovery.

Schlüsselwörter

DNA-encoded libraries - double-stranded DNA-encoded libraries - DNA-encoded benzimidazole libraries - DNA-compatible chemistry - benzimidazoles - headpiece DNA - DNA-recorded libraries - split-and-pool - chemical ligation - enzymatic ligation - building blocks - high-throughput screening - drug discovery

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