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

ABSTRACT: 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.

SUBMITTER: Qiu Z

PROVIDER: S-EPMC4983731 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Qiu Zongxing Z Kuhn Bernd B Aebi Johannes J Lin Xianfeng X Ding Haiyuan H Zhou Zheng Z Xu Zhiheng Z Xu Danqing D Han Li L Liu Cheng C Qiu Hongxia H Zhang Yuxia Y Haap Wolfgang W Riemer Claus C Stahl Martin M Qin Ning N Shen Hong C HC Tang Guozhi G

ACS medicinal chemistry letters 20160625 8

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. ...[more]

PMID: 27563406

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