title: Linkage effects on binding affinity and activation of GPR30 and estrogen receptors ERalpha/beta with tridentate pyridin-2-yl hydrazine tricarbonyl-Re/(99m)Tc(I) chelates.
abstract: We describe a new structural class of neutral tridentate pyridin-2-yl hydrazine chelates for labeling with tricarbonyl Re/99mTc(I) under aqueous conditions and investigate the receptor binding of synthetic estradiol derivatives with the novel G-protein-coupled receptor GPR30 and estrogen receptors ERalpha/beta. The steroid linkage affected the affinity and selectivity of estrogen binding with these receptors. Fluorescence assays based on calcium signaling demonstrate that membrane-permeable chelates 2 and 3 interact with the receptors in whole cells. These results suggest that in vitro assays will facilitate the development of targeted imaging agents for intracellular receptors and the feasibility of targeting GPR30 and ERalpha/beta for diagnostic tumor imaging.
authors.affiliation: Department of Chemistry and Biochemistry MSC 3C, New Mexico State University, P.O. Box 30001, Las Cruces, New Mexico 88003, USA.
authors.forename: Chinnasamy
authors.initials: C
authors.lastname: Ramesh
authors.forename: Bj
authors.initials: B
authors.lastname: Bryant
authors.forename: Tapan
authors.initials: T
authors.lastname: Nayak
authors.forename: Chetana M
authors.initials: CM
authors.lastname: Revankar
authors.forename: Tamara
authors.initials: T
authors.lastname: Anderson
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Carlson
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.forename: Larry A
authors.initials: LA
authors.lastname: Sklar
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Norenberg
authors.forename: Eric R
authors.initials: ER
authors.lastname: Prossnitz
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Arterburn
mesh_terms: D002614:Chelating Agents / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D009942:Organometallic Compounds / Q000378:metabolism*; D011485:Protein Binding; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C109584:GPER1 protein, human; D009942:Organometallic Compounds; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C523474:pyridin-2-yl hydrazine tricarbonyl-Re