title: Organometallic estrogens: synthesis, interaction with lamb uterine estrogen receptor, and detection by infrared spectroscopy.
abstract: As an integral part of the development of a new technique using organometallic markers for the detection of hormone receptors by FT-IR spectroscopy, a series of estradiol derivatives labeled with Cr(CO)3 or Cr(CO)2CS fragments on the A ring has been synthesized. The stereochemistry of one of these steroids, alpha-[3-(dimethyl-tert-butylsiloxy)-17 beta-estradiol]dicarbonyl(thiocarbonyl)chromium(0), has been established by X-ray diffraction. The organochromium-labeled steroids are stable in aqueous methanol solution, and their relative binding affinities to estrogen receptor have been determined; these values vary from 0.4 to 28%. The complex exhibiting the strongest affinity, [3-O-(3-hydroxypropyl)-17 beta-estradiol]-chromium tricarbonyl complex, has been prepared in a tritiated form with a high specific activity (4.1 Ci/mmol). This tritiated hormone binds reversibly to the estradiol receptor in lamb uterine cytosol with an affinity (Kd = 0.85 nM) and number of binding sites (n = 770 fmol/mg of protein) close to the values observed for estradiol itself. The level of nonspecific binding is low, and the hormone is not bound significantly to other nontarget tissues. The observation that the binding affinity of the steroid depends on which side of the steroidal A ring the organometallic label is bound demonstrates the nonequivalence of the two sides of the A ring with respect to the receptor site. The FT-IR spectra of the organochromium markers in the v(CO) region can be used for the detection of the estradiol receptor in lamb uterine cytosol.
authors.affiliation: Ecole Nationale Supérieure de Chimie de Paris, UA CNRS 403, France.
authors.forename: A
authors.initials: A
authors.lastname: Vessières
authors.forename: S
authors.initials: S
authors.lastname: Top
authors.forename: A A
authors.initials: AA
authors.lastname: Ismail
authors.forename: I S
authors.initials: IS
authors.lastname: Butler
authors.forename: M
authors.initials: M
authors.lastname: Louer
authors.forename: G
authors.initials: G
authors.lastname: Jaouen
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000378:metabolism*; D011959:Receptors, Estradiol / Q000378:metabolism*; D012756:Sheep; D013055:Spectrophotometry, Infrared; D014599:Uterus / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; D011959:Receptors, Estradiol; D004958:Estradiol