Abstract
Over the past 10 years, a handful of academic and industrial research groups have developed strategies for the synthesis and interrogation of DNA-encoded small-molecule libraries. These strategies can be divided into those in which DNA directs small-molecule synthesis and those in which it records the synthesis. These libraries have started to yield novel modulators of biological targets, including: SH3-domain-binding peptoids, macrocyclic peptide-based Bcl-X(L)/BH3 interaction disruptors, ligands for TNF, albumin, streptavidin and others, and small-molecule kinase inhibitors. The DNA-encoded library field holds the potential to address the general problem of biological ligand discovery, including pharmaceutical lead generation.
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