Backbone thioamide directed macrocyclisation: lactam stapling of peptides

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 generate...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2022-02, Vol.20 (7), p.1488-1492
Main Authors: Taresh, Ameer B, Hutton, Craig A
Format: Article
Language:English
Subjects:
Amides
Backbone
Coupling agents
Lactams - chemistry
Macromolecular Substances - chemical synthesis
Macromolecular Substances - chemistry
Molecular Structure
Peptides
Peptides, Cyclic - chemical synthesis
Peptides, Cyclic - chemistry
Thioamides - chemistry
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Summary: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 , +2, , +3, and , +4-spaced lactam-bridged peptides.
ISSN:1477-0520
1477-0539
DOI:10.1039/d1ob02461b