On the design of lead-like DNA-encoded chemical libraries

Photoredox-catalysed hydroaminoalkylation of on-DNA N-arylamines

“…3 However, due to the chemical restrictions imposed by the DNA barcode and conventional aqueous solvents, 4 DELs continue to be limited by their chemical space and molecular properties, particularly when compared against traditional screening libraries. 5 Chemists have sought to develop new DEL-compatible chemistries to facilitate the generation of more diverse chemical libraries with drug-like properties. To this end, the last decade has witnessed an explosive growth in available DEL chemistry, 6 including medicinal chemistry staples, such as Suzuki-Miyaura coupling 7 and Buchwald-Hartwig amination.…”

Micellar Buchwald–Hartwig Coupling of Aryl and Heteroarylamines for the Synthesis of DNA-Encoded Libraries

“…DNA-encoded libraries (DELs) have attracted much attention in recent years as an efficient means to identify hit compounds for a drug discovery campaign. − DELs are mixtures of DNA-tagged small molecules, in which the DNA tag is unique to the chemical structure that it encodes. Typically, these libraries are synthesized using multiple cycles of split and pool combinatorial synthesis, in which each chemical monomer coupling is accompanied by the attachment of an encoding DNA oligomer that is unique to each monomer (Figure ).…”

Functional Group Tolerance of a Micellar on-DNA Suzuki–Miyaura Cross-Coupling Reaction for DNA-Encoded Library Design

“…A screening technology that has gained in prominence in recent years is DNA-encoded libraries (DELs). − These libraries are synthesized by combinatorial cycles of organic transformations and enzymatic barcode ligation. Unlike traditional screening libraries, which typically consist of compounds stored individually, DELs are efficiently handled and screened against target proteins as complex pools of encoded compounds.…”