Preparation, receptor binding, and fluorescence properties of hexestrol-fluorophore conjugates: evaluation of site of attachment, fluorophore structure, and fluorophore-ligand spacing.
We have undertaken a staged development of certain estrogen-fluorophore conjugates, in order to prepare a fluorescent estrogen suitable for determination of the estrogen receptor content of individual cells. Since non-steroidal estrogens with bulky substituents are often more readily bound by receptor than their steroidal counterparts, we have investigated fluorophore conjugates with derivatives of the non-steroidal estrogen hexestrol [3R*, 4S*)-3,4-bis(4-hydroxyphenyl)hexane). On the basis of the receptor-binding affinity of model compounds, we prepared a prototypical set of three ring- and side-chain-substituted fluorescent hexestrol derivatives, whose binding and fluorescence properties ultimately led to the preparation of a series of side-chain-substituted nitrobenzoxadiazole derivatives. The compounds prepared have binding affinities for the estrogen receptors that range from ca. 1% to 5% that of estradiol, and they have very favorable fluorescence characteristics, similar to those of fluorescein.
D000818:Animals; D004958:Estradiol / Q000378:metabolism; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000378:metabolism; D006589:Hexestrol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011960:Receptors, Estrogen / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D011960:Receptors, Estrogen; D006589:Hexestrol; D004958:Estradiol