title: Novel estradiol derivatives labeled with Ru, W, and Co complexes. Influence on hormone-receptor affinity of several organometallic groups at the 17 alpha position.
abstract: In order to elucidate the extent to which recognition of the estrogen receptor is influenced by addition of an organometallic substituent at the 17 alpha position, modification of 17 beta-estradiol at this position was carried out by using the organometallic groups -C identical to C(eta 5-C5H4)RuCp, CH2-(eta 5-C5H4)RuCp, -C identical to C-(eta 5-C5H4)-W(CO)3(Me), -(C identical to CCHO)Co2(CO)6, and -(C identical to CCH2OH)Co2(CO)6. The relative binding affinity (RBA) values for estradiol receptor alpha showed that recognition was good (RBA between 20 and 13.5%) when the organometallic moiety was attached at the end of a rigid alkyne spacer. However, the affinity of the modified hormone for the receptor was severely reduced (RBA = 1%) for a substituent such as -CH2-(eta 5-C5H4)RuCP, in which the spacer is reduced to a single flexible sp3 carbon atom, allowing the organometallic moiety greater freedom of movement around the attachment point. The RBA values found were in agreement with results obtained from a molecular-modeling study in which 5, an organometallic hormone with a rigid spacer, or 7, a molecule with a flexible spacer, was inserted into the cavity of the recently characterized Ligand-Binding Domain of estrogen receptor alpha.
authors.affiliation: Laboratoire de Chimie Organométallique Ecole Nationale Supérieure de Chimie de Paris, UMR C.N.R.S. 7576 11, rue Pierre et Marie Curie, 75231, Paris, France. siden@ext.jussieu.fr, jaouen@ext.jussieu.fr
authors.forename: Siden
authors.initials: S
authors.lastname: Top
authors.forename: Hassane
authors.initials: H
authors.lastname: el Hafa
authors.forename: Anne
authors.initials: A
authors.lastname: Vessiéres
authors.forename: Michel
authors.initials: M
authors.lastname: Huché
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vaissermann
authors.forename: Gérard
authors.initials: G
authors.lastname: Jaouen
mesh_terms: D000818:Animals; D001665:Binding Sites; D003035:Cobalt / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D047628:Estrogen Receptor alpha; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D012428:Ruthenium / Q000737:chemistry / Q000378:metabolism*; D012756:Sheep; D014414:Tungsten / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D003035:Cobalt; D004958:Estradiol; D012428:Ruthenium; D014414:Tungsten