荧光素衍生物作为双功能分子，可同时抑制和标记 FTO 蛋白。
Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein.
机构信息
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
School of Life Sciences, Fudan University , Shanghai 200433, China.
出版信息
J Am Chem Soc. 2015 Nov 4;137(43):13736-9. doi: 10.1021/jacs.5b06690. Epub 2015 Oct 20.
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.
FTO 蛋白被明确报道在人类肥胖和细胞内 m(6)A 修饰水平的调控中发挥关键作用，这使得 FTO 成为一个重要且值得研究的对象。在这里，我们发现荧光素衍生物可以选择性地抑制 FTO 的去甲基化，并且在确定了 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，这些抑制剂还可以与光亲和标记测定法结合，应用于 FTO 蛋白的直接标记和富集。
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