Fluorescent Ligand for Human Progesterone Receptor Imaging in Live Cells

详细信息    查看全文

• 作者：Roy Weinstain ; Joan Kanter ; Beth Friedman ; Lesley G. Ellies ; Michael E. Baker ; Roger Y. Tsien
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：May 15, 2013
• 年：2013
• 卷：24
• 期：5
• 页码：766-771
• 全文大小：314K
• 年卷期：v.24,no.5(May 15, 2013)
• ISSN：1520-4812

文摘

We employed molecular modeling to design and then synthesize fluorescent ligands for the human progesterone receptor. Boron dipyrromethene (BODIPY) or tetramethylrhodamine were conjugated to the progesterone receptor antagonist RU486 (Mifepristone) through an extended hydrophilic linker. The fluorescent ligands demonstrated comparable bioactivity to the parent antagonist in live cells and triggered nuclear translocation of the receptor in a specific manner. The BODIPY labeled ligand was applied to investigate the dependency of progesterone receptor nuclear translocation on partner proteins and to show that functional heat shock protein 90 but not immunophilin FKBP52 activity is essential. A tissue distribution study indicated that the fluorescent ligand preferentially accumulates in tissues that express high levels of the receptor in vivo. The design and properties of the BODIPY-labeled RU486 make it a potential candidate for in vivo imaging of PR by positron emission tomography through incorporation of ¹⁸F into the BODIPY core.