Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein.
Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein.
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DOI：
10.1021/jacs.5b06690
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发表时间：
2015-10
影响因子：
15
通讯作者：
Tianlu Wang;Tingting Hong;Yue Huang;Haomiao Su;Fan Wu;Yi Chen;Lai Wei;Wei Huang;Xiaoluan Hua-Xiao
中科院分区：
文献类型：
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作者：
Tianlu Wang;Tingting Hong;Yue Huang;Haomiao Su;Fan Wu;Yi Chen;Lai Wei;Wei Huang;Xiaoluan Hua-Xiao
据明确报道，FTO 蛋白在人类肥胖和 m(6)A 修饰细胞水平的调节中发挥着关键作用，这使得 FTO 成为一个重要且值得研究的课题。在这里，我们发现荧光素衍生物可以选择性抑制FTO去甲基化，并在确定FTO/荧光素和FTO/5-氨基荧光素的X射线晶体结构后阐明了这些活性背后的机制。此外，这些抑制剂还可以结合光亲和标记测定应用于FTO蛋白的直接标记和富集。
The FTO protein is unequivocally reported to play a critical role in human obesity and in the regulation of cellular levels of m(6)A modification, which makes FTO a significant and worthy subject of study. Here, we identified that fluorescein derivatives can selectively inhibit FTO demethylation, and the mechanisms behind these activities were elucidated after we determined the X-ray crystal structures of FTO/fluorescein and FTO/5-aminofluorescein. Furthermore, these inhibitors can also be applied to the direct labeling and enrichment of FTO protein combined with photoaffinity labeling assay.