Ramesh Chinnasamy, Bryant Bj, Nayak Tapan, Revankar Chetana M, Anderson Tamara, Carlson Kathryn E, Katzenellenbogen John A, Sklar Larry A, Norenberg Jeffrey P, Prossnitz Eric R, Arterburn Jeffrey B
Department of Chemistry and Biochemistry MSC 3C, New Mexico State University, P.O. Box 30001, Las Cruces, New Mexico 88003, USA.
J Am Chem Soc. 2006 Nov 15;128(45):14476-7. doi: 10.1021/ja066360p.
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.
我们描述了一类新型的中性三齿吡啶 - 2 - 基肼螯合物，用于在水性条件下用三羰基铼/锝 - 99m（I）进行标记，并研究了合成雌二醇衍生物与新型G蛋白偶联受体GPR30和雌激素受体ERα/β的受体结合情况。甾体连接影响了雌激素与这些受体结合的亲和力和选择性。基于钙信号的荧光测定表明，膜通透性螯合物2和3在全细胞中与受体相互作用。这些结果表明，体外测定将有助于开发用于细胞内受体的靶向成像剂，以及靶向GPR30和ERα/β用于诊断肿瘤成像的可行性。
