Naphthalimide Scaffold Provides Versatile Platform for Selective Thiol Sensing and Protein Labeling

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• 作者：Pengcheng Zhou ; Juan Yao ; Guodong Hu ; Jianguo Fang
• 刊名：ACS Chemical Biology
• 出版年：2016
• 出版时间：April 15, 2016
• 年：2016
• 卷：11
• 期：4
• 页码：1098-1105
• 全文大小：556K
• 年卷期：0
• ISSN：1554-8937

文摘

Reversible thiol modifications are fundamental of cellular redox regulation. Specific thiol detection, including thiol sensing and protein thiols labeling, is critical to study such modifications. We reported the discovery of 4-methylsulfonyl-N-n-butyl-1,8-naphthalimide (MSBN), a highly selective fluorogenic probe for thiols based on the 1,8-naphthalimide scaffold. Thiols react with MSBN nearly quantitatively via nucleophilic aromatic substitution to replace the methylsulfonyl group and restore the quenched fluorescence (>100-fold increase). MSBN was employed to selectively image thiols in live cells and specifically label protein thiols with a turn-on signal to determine diverse reversible protein thiol modifications. In addition, we introduced a bulky group into the MSBN as a mass tag to create a probe MSBN-TPP, which readily discriminates the reduced thioredoxin from the oxidized one. The specific reaction of MSBN with thiols and the easy manipulation of the naphthalimide unit enable MSBN a versatile scaffold in developing novel probes for thiol-based protein bioconjugation and studying various thiol modifications.