1. Synthesis of maleimide-braced peptide macrocycles and their potential anti-SARS-CoV-2 mechanisms.
- Author
-
Li, Jian, Sun, Jina, Zhang, Xianglei, Zhang, Ruxue, Wang, Qian, Wang, Lin, Zhang, Leike, Xie, Xiong, Li, Chunpu, Zhou, Yu, Wang, Jiang, Xiao, Gengfu, Bai, Fang, and Liu, Hong
- Subjects
PEPTIDE synthesis ,PEPTIDES ,PEPTIDOMIMETICS ,CARRIER proteins ,ALKENYLATION ,TRP channels - 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 CāH 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 EC
50 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. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF