Issue 16, 2021

Streamlined construction of peptide macrocycles via palladium-catalyzed intramolecular S-arylation in solution and on DNA

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.

Graphical abstract: Streamlined construction of peptide macrocycles via palladium-catalyzed intramolecular S-arylation in solution and on DNA

Supplementary files

Article information

Article type
Edge Article
Submitted
08 2月 2021
Accepted
08 3月 2021
First published
11 3月 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 5804-5810

Streamlined construction of peptide macrocycles via palladium-catalyzed intramolecular S-arylation in solution and on DNA

P. Yang, X. Wang, B. Li, Y. Yang, J. Yue, Y. Suo, H. Tong, G. He, X. Lu and G. Chen, Chem. Sci., 2021, 12, 5804 DOI: 10.1039/D1SC00789K

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