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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chelating Agents / metabolism*
  • Estrogen Receptor alpha / metabolism*
  • Estrogen Receptor beta / metabolism*
  • Organometallic Compounds / metabolism*
  • Protein Binding
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Chelating Agents
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • GPER1 protein, human
  • Organometallic Compounds
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • pyridin-2-yl hydrazine tricarbonyl-Re