Discovery of Fluoromethylketone-Based Peptidomimetics as Covalent ATG4B (Autophagin-1) Inhibitors

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• 作者：Zongxing Qiu ; Bernd Kuhn ; Johannes Aebi ; Xianfeng Lin ; Haiyuan Ding ; Zheng Zhou ; Zhiheng Xu ; Danqing Xu ; Li Han ; Cheng Liu ; Hongxia Qiu ; Yuxia Zhang ; Wolfgang Haap ; Claus Riemer ; Martin Stahl ; Ning Qin ; Hong C. Shen ; Guozhi Tang
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：August 11, 2016
• 年：2016
• 卷：7
• 期：8
• 页码：802-806
• 全文大小：399K
• 年卷期：0
• ISSN：1948-5875

文摘

ATG4B or autophagin-1 is a cysteine protease that cleaves ATG8 family proteins. ATG4B plays essential roles in the autophagosome formation and the autophagy pathway. Herein we disclose the design and structural modifications of a series of fluoromethylketone (FMK)-based peptidomimetics as highly potent ATG4B inhibitors. Their structure–activity relationship (SAR) and protease selectivity are also discussed.