Mechanically Triggered Protein Desulfurization

IF 14.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Dongyang Han, Yan Cui, Xiangyu Deng, Chuntong Li, Xianglai Zhu, Bingji Wang, Guo-Chao Chu, Zhipeng A. Wang, Shan Tang, Ji-Shen Zheng, Lu-Jun Liang, Lei Liu
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引用次数: 0

Abstract

The technology of native chemical ligation and postligation desulfurization has greatly expanded the scope of modern chemical protein synthesis. Here, we report that ultrasonic energy can trigger robust and clean protein desulfurization, and we developed an ultrasound-induced desulfurization (USID) strategy that is simple to use and generally applicable to peptides and proteins. The USID strategy involves a simple ultrasonic cleaning bath and an easy-to-use and easy-to-remove sonosensitizer, titanium dioxide. It features mild and convenient reaction conditions and excellent functional group compatibility, e.g., with thiazolidine (Thz) and serotonin, which are sensitive to other desulfurization strategies. The USID strategy is robust: without reoptimizing the reaction conditions, the same USID procedure can be used for the clean desulfurization of a broad range of proteins with one or more sulfhydryl groups, even in multi-hundred-milligram scale reactions. The utility of USID was demonstrated by the one-pot synthesis of bioactive cyclopeptides such as Cycloleonuripeptide E and Segetalin F, as well as convergent chemical synthesis of functionally important proteins such as histone H3.5 using Thz as a temporary protecting group. A mechanistic investigation indicated that USID proceeds via a radical-based mechanism promoted by low-frequency and low-intensity ultrasonication. Overall, our work introduces a mechanically triggered approach with the potential to become a robust desulfurization method for general use in chemical protein synthesis by both academic and industrial laboratories.

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来源期刊
CiteScore
24.40
自引率
6.00%
发文量
2398
审稿时长
1.6 months
期刊介绍: The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.
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