title: Fluorescent ligand for human progesterone receptor imaging in live cells.
abstract: 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 (18)F into the BODIPY core.
authors.affiliation: Department of Pharmacology 0647, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Weinstain
authors.forename: Joan
authors.initials: J
authors.lastname: Kanter
authors.forename: Beth
authors.initials: B
authors.lastname: Friedman
authors.forename: Lesley G
authors.initials: LG
authors.lastname: Ellies
authors.forename: Michael E
authors.initials: ME
authors.lastname: Baker
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Tsien
mesh_terms: D001896:Boron Compounds / Q000032:analysis* / Q000378:metabolism; D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis* / Q000378:metabolism; D006727:Hormone Antagonists / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D015735:Mifepristone / Q000032:analysis* / Q000378:metabolism; D008958:Models, Molecular; D061848:Optical Imaging; D011980:Receptors, Progesterone / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes; D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D015735:Mifepristone