biostudies-literatureYang PNatural Science Foundation of Tianjin CityMinistry of Education of the People&apos;s Republic of ChinaNational Natural Science Foundation of China5804-5810https://www.ebi.ac.uk/biostudies/studies/S-EPMC8179660biostudies-literatureUnknown12(16)A highly efficient and versatile method for construction of peptide macrocycles <i>via</i> palladium-catalyzed intramolecular <i>S</i>-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.Chemical scienceStreamlined construction of peptide macrocycles <i>via</i> palladium-catalyzed intramolecular <i>S</i>-arylation in solution and on DNA.PMC8179660B060052187711721672105917531242172520418JCZDJC3280091953203Yang YLu XHe GYang PChen GTong HWang XLi BSuo YYue JfalseStreamlined construction of peptide macrocycles <i>via</i> palladium-catalyzed intramolecular <i>S</i>-arylation in solution and on DNA.A highly efficient and versatile method for construction of peptide macrocycles <i>via</i> palladium-catalyzed intramolecular <i>S</i>-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.2021-01-01T00:00:00Z2021 Mar2025-04-04T03:21:06.577Z2022-02-10T15:58:36.873ZS-EPMC81796603416880410.1039/d1sc00789k