Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein

  • J Am Chem Soc. 2015 Nov 4;137(43):13736-9. doi: 10.1021/jacs.5b06690.
Tianlu Wang ,  Tingting Hong ,  Yue Huang  1 ,  Haomiao Su ,  Fan Wu ,  Yi Chen ,  Lai Wei ,  Wei Huang ,  Xiaoluan Hua ,  Yu Xia ,  Jinglei Xu ,  Jianhua Gan  2 ,  Bifeng Yuan ,  Yuqi Feng ,  Xiaolian Zhang ,  Cai-Guang Yang  1 ,  Xiang Zhou
Affiliations
  • 1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
  • 2. School of Life Sciences, Fudan University , Shanghai 200433, China.
PMID: 26457839 DOI: 10.1021/jacs.5b06690
Abstract

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.

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