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Published on: January 26, 2016
Synthesis of a DNA-Encoded Macrocyclic Library Utilizing Intramolecular Benzimidazole Formation
Jing Chai1, Christopher C Arico-Muendel1, Yun Ding1
1Encoded Library Technologies/NCE Molecular Discovery, GSK, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, United States.
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.
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