期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 53, 期 44, 页码 11969-11973出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201406964
关键词
drug design; inhibitors; immunoproteasome; peptido sulfonyl fluoride; umpolung
资金
- SFB [1035A2]
- DFG GR [1861/10-1]
The concept of proteasome inhibition ranks among the latest achievements in the treatment of blood cancer and represents a promising strategy for modulating autoimmune diseases. In this study, we describe peptidic sulfonyl fluoride inhibitors that selectively block the catalytic beta 5 subunit of the immunoproteasome by inducing only marginal cytotoxic effects. Structural and mass spectrometric analyses revealed a novel reaction mechanism involving polarity inversion and irreversible crosslinking of the proteasomal active site. We thus identified the sulfonyl fluoride headgroup for the development and optimization of immunoproteasome selective compounds and their possible application in autoimmune disorders.
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