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.
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.
Ramesh
Chinnasamy
C
Department of Chemistry and Biochemistry MSC 3C, New Mexico State University, P.O. Box 30001, Las Cruces, New Mexico 88003, USA.
Bryant
Bj
B
Nayak
Tapan
T
Revankar
Chetana M
CM
Anderson
Tamara
T
Carlson
Kathryn E
KE
Katzenellenbogen
John A
JA
Sklar
Larry A
LA
Norenberg
Jeffrey P
JP
Prossnitz
Eric R
ER
Arterburn
Jeffrey B
JB
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*
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