期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 143, 期 35, 页码 14322-14331出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c06565
关键词
-
资金
- Alexander von Humboldt Foundation
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [RTG 2473]
The study presents an efficient method for constructing tryptathionine-cross-links in peptides between tryptophan and cysteine, which is essential for synthesizing alpha-amanitin and new amanitin analogues. It also provides a systematic compilation of structure-activity relations of amatoxins, showing potential for synthesizing structurally diverse amatoxins as future payloads for antibody-toxin conjugates in cancer therapy.
Synthetic methods on the macrocyclization of peptides are of high interest since they facilitate the synthesis of various types of potentially bioactive compounds, e.g. addressing targets like protein-protein-interactions. Herein, we report on an efficient method to construct tryptathionine-cross-links in peptides between the amino acids Trp and Cys. This reaction not only is the basis for the total synthesis of the death cap toxin alpha-amanitin but also provides rapid access to various new amanitin analogues. This study for the first time presents a systematic compilation of structure-activity relations (SAR) of amatoxins with regard to RNA polymerase II inhibition and cytotoxicity with one amanitin derivative of superior RNAP II inhibition. The present approach paves the way for the synthesis of structurally diverse amatoxins as future payloads for antibody-toxin conjugates in cancer therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据