title: Organometallic derivatives of estradiol as bioligands: targetted binding of the estradiol receptor.
abstract: The complexation of estrogens by transitional metal units e.g. (alkyne)Co2(CO)6 and (alkyne)Mo2Cp2(CO)4, at the 17 alpha-position brings about a dramatic change in the chemical behavior of these compounds with respect to that of the free ligands. The 17 beta-OH function becomes particularly labile, even in weakly acidic medium, giving rise to carbenium ion-like species, from which, depending on the metal and the nucleophile, substitution, elimination and rearrangement take place. This situation provides the basis for a new type of active site directed-reagent for estradiol receptor. The hypothesis of vicinal space positioning of an acidic and a nucleophilic group in the estradiol receptor cavity is examined in the light of the amino-acid composition of the steroid binding domain. The requirement of the sulfhydryl group of a cysteine residue is suspected in the first step of the receptor inactivation process.
authors.affiliation: Ecole Nationale Supérieure de Chimie de Paris, U.R.A. C.N.R.S. 403, France.
authors.forename: A
authors.initials: A
authors.lastname: Vessières
authors.forename: C
authors.initials: C
authors.lastname: Vaillant
authors.forename: M
authors.initials: M
authors.lastname: Salmain
authors.forename: G
authors.initials: G
authors.lastname: Jaouen
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008024:Ligands; D009942:Organometallic Compounds / Q000494:pharmacology*; D011959:Receptors, Estradiol / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects; D012756:Sheep; D014599:Uterus / Q000378:metabolism*
chemical_list: D004963:Estrenes; D008024:Ligands; D009942:Organometallic Compounds; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; C063184:17-propynylestra-1,3,5-triene-3,17-diol dicyclopentadienyl dimolybdenum tetracarbonyl; C063183:17-propynylestra-1,3,4(10)-triene-3,17-diol dicobalt hexacarbonyl; D004958:Estradiol; D005033:Ethylmaleimide