Issue 7, 2023

Synthesis of maleimide-braced peptide macrocycles and their potential anti-SARS-CoV-2 mechanisms

Abstract

Macrocycles often exhibit good biological properties and potential druggability, which lead to versatile applications in the pharmaceutical industry. Herein, we report a highly efficient and practical methodology for the functionalization and macrocyclization of Trp and Trp-containing peptides via Pd(II)-catalyzed Cā€“H alkenylation at the Trp C4 position. This method provides direct access to C4 maleimide-decorated Trp-containing peptidomimetics and maleimide-braced 17- to 30-membered peptide macrocycles. In particular, these unique macrocycles revealed low micro- to sub-micromolar EC50 values with promising anti-SARS-CoV-2 activities. Further explorations with computational methodologies and experimental validations indicated that these macrocycles exert antiviral effects through binding with the N protein of SARS-CoV-2.

Graphical abstract: Synthesis of maleimide-braced peptide macrocycles and their potential anti-SARS-CoV-2 mechanisms

Supplementary files

Article information

Article type
Communication
Submitted
24 Nov 2022
Accepted
09 Dec 2022
First published
12 Dec 2022

Chem. Commun., 2023,59, 868-871

Synthesis of maleimide-braced peptide macrocycles and their potential anti-SARS-CoV-2 mechanisms

J. Li, J. Sun, X. Zhang, R. Zhang, Q. Wang, L. Wang, L. Zhang, X. Xie, C. Li, Y. Zhou, J. Wang, G. Xiao, F. Bai and H. Liu, Chem. Commun., 2023, 59, 868 DOI: 10.1039/D2CC06371A

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