School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.
Org Biomol Chem. 2022 Feb 16;20(7):1488-1492. doi: 10.1039/d1ob02461b.
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.
现已开发出一种用于含有 Asp/Lys 的肽的新型环内酰胺键合方法，该方法无需使用偶联剂。在天冬氨酸残基的 N 端侧引入了硫代酰胺。Ag（I）促进了天冬氨酸羧酸盐附近的硫代酰胺的活化，生成环状异亚氨酸中间体，该中间体被赖氨酸的胺捕获，生成大环内酰胺。该方法适用于生成,+2,,+3, 和,+4-间隔的环内酰胺桥接肽。
