Synthesis of a DNA-Encoded Macrocyclic Library Utilizing Intramolecular Benzimidazole Formation

Bioconjug Chem. 2023 Jun 21;34(6):988-993. doi: 10.1021/acs.bioconjchem.3c00159. Epub 2023 May 22.

Abstract

Macrocycles occupy chemical space "beyond the rule of five". They bridge traditional bioactive small molecule drugs and macromolecules and have the potential to modulate challenging targets such as PPI or proteases. Here we report an on-DNA macrocyclization reaction utilizing intramolecular benzimidazole formation. A 129-million-member macrocyclic library composed of a privileged benzimidazole core, a dipeptide sequence (natural or non-natural), and linkers of varying length and flexibility was designed and synthesized.

MeSH terms

  • Benzimidazoles
  • Cyclization
  • DNA / chemistry
  • Gene Library
  • Macrocyclic Compounds* / chemistry

Substances

  • Macrocyclic Compounds
  • Benzimidazoles
  • DNA