Streamlined construction of peptide macrocycles <i>via</i> palladium-catalyzed intramolecular <i>S</i>-arylation in solution and on DNA
Peng Yang, Xuan Wang, Bo Li, Yixuan Yang, Jinfeng Yue, Yanrui Suo, Huarong Tong, Gang He, Xiaojie Lu, Gong Chen
Abstract
-arylation of alkyl and aryl thiols with aryl iodides under mild conditions is developed. The method exhibits a broad substrate scope for thiols, aryl iodides and amino acid units. Peptide macrocycles of a wide range of size and composition can be readily assembled in high yield from various easily accessible building blocks. This method has been successfully employed to prepare an 8-million-membered tetrameric cyclic peptide DNA-encoded library (DEL). Preliminary screening of the DEL library against protein p300 identified compounds with single digit micromolar inhibition activity.
Topics & Concepts
Intramolecular forcePalladiumCatalysisPeptideChemistryCombinatorial chemistryDNAStereochemistryOrganic chemistryBiochemistrySulfur-Based Synthesis TechniquesChemical Synthesis and AnalysisClick Chemistry and Applications