title: [125I]iododesethyl tamoxifen aziridine: synthesis and covalent labeling of the estrogen receptor with an iodine-labeled affinity label.
abstract: Iododesethyl tamoxifen aziridine (I-Tam-Az), an analog of the estrogen receptor-affinity label tamoxifen aziridine (Tam-Az) in which the ethyl group has been replaced by an iodine, has been prepared by two routes: (a) metallation of a bromotriarylethylene system, followed by reaction with iodine, and aziridinylation, and (b) direct iodination of a trimethylstannyl triarylethylene system that is the immediate precursor of I-Tam-Az. The latter method can be used to prepare [125I]I-Tam-Az rapidly and in good yield, both at carrier-added and no-carrier-added levels; specific activities greater than 200 Ci/mmol have been obtained. In competitive radiometric binding assays with the estrogen receptor, I-Tam-Az has an apparent affinity of ca. 20%, equivalent to that of Tam-Az. It also undergoes rapid and selective time-dependent, irreversible binding to the estrogen receptor. [125I]I-Tam-Az reacts covalently with estrogen receptor in uterine cytosol preparations; its attachment is rapid and efficient, but somewhat less selective than that of Tam-Az. Estrogen receptor in intact MCF-7 human breast cancer cells can also be labeled with [125I]I-Tam-Az, and autoradiographic analysis of salt extracts of labeled nuclear estrogen receptor on SDS-polyacrylamide slab gels shows highly selective labeling of a 65K protein. [125I]I-Tam-Az is an efficient, selective affinity label for the estrogen receptor, available at high specific activity, and should be useful in studies on estrogen receptor structure, dynamics, and chromatin interactions.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana 61801.
authors.forename: F G
authors.initials: FG
authors.lastname: Salituro
authors.forename: K E
authors.initials: KE
authors.lastname: Carlson
authors.forename: J F
authors.initials: JF
authors.lastname: Elliston
authors.forename: B S
authors.initials: BS
authors.lastname: Katzenellenbogen
authors.forename: J A
authors.initials: JA
authors.lastname: Katzenellenbogen
mesh_terms: D000345:Affinity Labels; D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D002855:Chromatography, Thin Layer; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007457:Iodine Radioisotopes; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D012756:Sheep; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D014599:Uterus / Q000166:cytology / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D013629:Tamoxifen; C055269:iododesethyltamoxifen aziridine