Streamlined construction of peptide macrocycles via palladium-catalyzed intramolecular S-arylation in solution and on DNA |
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| Authors: | Peng Yang Xuan Wang Bo Li Yixuan Yang Jinfeng Yue Yanrui Suo Huarong Tong Gang He Xiaojie Lu Gong Chen |
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| Institution: | State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071 China.; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203 China, |
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| 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.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. |
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