Preparation, Receptor Binding, and Fluorescence Properties of Hexestrol-Fluorophore Conjugates: Evaluation of Site of Attachment, Fluorophore Structure, and Fluorophore-Ligand Spacing

Article abstract of DOI:10.1021/jm00384a026

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. 1percent to 5percent that of estradiol, and they have very favorable fluorescence characteristics, similar to those of fluorescein.