Peng Yang; Xuan Wang; Bo Li; Yixuan Yang; Jinfeng Yue; Yanrui Suo; Huarong Tong; Gang He; Xiaojie Lu; Gong Chen
Chem. Sci., 2021, 12, 5804-5810
https://doi.org/10.1039/D1SC00789K

Abstract

A highly efficient and versatile method for construction of peptide macrocycles via palladium-catalyzed intramolecular S-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.