Issue 7, 2022

Backbone thioamide directed macrocyclisation: lactam stapling of peptides

Abstract

A novel method for lactam stapling of Asp/Lys-containing peptides has been developed that does not require coupling agents. A backbone thioamide is incorporated at the N-terminal side of the aspartate residue. Ag(I)-promoted activation of the thioamide in the vicinity of the Asp carboxylate generates a cyclic isoimide intermediate that is trapped by the Lys amine to generate the macrolactam. This method is suitable for generation of i,i+2, i,i+3, and i,i+4-spaced lactam-bridged peptides.

Graphical abstract: Backbone thioamide directed macrocyclisation: lactam stapling of peptides

Supplementary files

Article information

Article type
Paper
Submitted
21 Dec 2021
Accepted
20 Jan 2022
First published
21 Jan 2022

Org. Biomol. Chem., 2022,20, 1488-1492

Backbone thioamide directed macrocyclisation: lactam stapling of peptides

A. B. Taresh and C. A. Hutton, Org. Biomol. Chem., 2022, 20, 1488 DOI: 10.1039/D1OB02461B

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