Synthesis and evaluation of a fluorescent non-peptidic cholecystokinin-B/gastrin receptor specific antagonist for cancer cell imaging |
| |
Authors: | Kumari Saroj Chowdhury Joyita Mishra Anil K Chandna Sudhir Saluja Daman Chopra Madhu |
| |
Affiliation: | Dr. BR Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India. |
| |
Abstract: | Fluorescent labeling has enabled a better understanding of the relationships between receptor location, function, and life cycle. Each of these perspectives contributes new insights into drug action, particularly for G protein‐coupled receptors (GPCRs). The aim of this study was to develop a fluorescein derivative, FLUO‐QUIN—a novel antagonist of the cholecystokinin‐B/gastrin receptor. A radioligand‐binding experiment revealed an IC50 of 4.79 nm, and the antagonist inhibited gastric acid secretion in an isolated lumen‐perfused mouse stomach assay (up to 51 % at 100 nm) . The fluorescence properties altered upon binding to the receptor, and the fluorophore was quenched to a greater extent when free than in the bound form. FLUO‐QUIN specifically bound to human pancreatic carcinoma cells, MiaPaca‐2, which are known to express the receptor, as evidenced by rapid clustering followed by time‐dependent receptor internalization. This proves the stability of FLUO‐QUIN and its ability to penetrate vesicular membranes and reach various cell targets. Hence it might be used as an agent for the detection of CCK‐B‐receptor‐positive tumors by fluorescence imaging. |
| |
Keywords: | emission spectroscopy fluorescent probes G protein‐coupled receptors synthesis design thiocarbonyl heterocyclic compound |
本文献已被 PubMed 等数据库收录! |
|