Profiling Sulfur(VI) Fluorides as Reactive Functionalities for Chemical Biology Tools and Expansion of the Ligandable Proteome.

Profiling Sulfur(VI) Fluorides as Reactive Functionalities for Chemical Biology Tools and Expansion of the Ligandable Proteome.
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DOI:
10.1021/acschembio.2c00633
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发表时间:
2023-02-17
影响因子:
4
通讯作者:
Bush JT
Bush JT
中科院分区:
生物学2区
文献类型:
--
作者:
Gilbert KE;Vuorinen A;Aatkar A;Pogány P;Pettinger J;Grant EK;Kirkpatrick JM;Rittinger K;House D;Burley GA;Bush JT

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在这里,我们报告了硫(VI)氟化物(SVI-Fs)作为化学生物学应用的活性基团的综合分析。SVI-F是修饰赖氨酸、酪氨酸、组氨酸和丝氨酸侧链的反应性官能团。研究了一组SVI-Fs与亲核氨基酸侧链的水解性和反应性。然后研究了使用SVI-Fs共价修饰碳酸氢酶II(CAII)和一系列的酶。最后,SVI-F面板被用于活细胞化学蛋白质组工作流程,根据所使用的SVI-F类型识别新的蛋白质靶点。这项工作突出了SVI-F反应性如何可以作为一种工具来扩展连接的蛋白质组。
Here, we report a comprehensive profiling of sulfur(VI) fluorides (SVI-Fs) as reactive groups for chemical biology applications. SVI-Fs are reactive functionalities that modify lysine, tyrosine, histidine, and serine sidechains. A panel of SVI-Fs were studied with respect to hydrolytic stability and reactivity with nucleophilic amino acid sidechains. The use of SVI-Fs to covalently modify carbonic anhydrase II (CAII) and a range of kinases was then investigated. Finally, the SVI-F panel was used in live cell chemoproteomic workflows, identifying novel protein targets based on the type of SVI-F used. This work highlights how SVI-F reactivity can be used as a tool to expand the liganded proteome.
化学蛋白质组学的共价配体筛选显示ALDH3A1是肺癌治疗靶标。
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