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. 2006 Nov 15;128(45):14476-7.
doi: 10.1021/ja066360p.

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

Chinnasamy Ramesh  1 , Bj Bryant, Tapan Nayak, Chetana M Revankar, Tamara Anderson, Kathryn E Carlson, John A Katzenellenbogen, Larry A Sklar, Jeffrey P Norenberg, Eric R Prossnitz, Jeffrey B Arterburn
Affiliations

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

Chinnasamy Ramesh et al. J Am Chem Soc. .

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.

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Figures

Figure 1
Figure 1
X-ray ORTEP rendition of complex 1
Fig 2
Fig 2
Fluorescence assays for GPR30 binding and activation with 2 and 3. a) GPR30 competitive binding of E2, 17α-E2, 2, and 3 with fluorescent estradiol derivative E2Alexa using permeabilized COS7 cells. b) Calcium mobilization assay for GPR30 and ERα in transfected COS7 cells vs concentration of E2, and complexes 2 and 3 (each at 10, 100, and 1000 nM).
See this image and copyright information in PMC

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