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Synthesis and Evaluation of a Fluorescent Non‐Peptidic Cholecystokinin‐B/Gastrin Receptor Specific Antagonist for Cancer Cell Imaging
Author(s) -
Kumari Saroj,
Chowdhury Joyita,
Mishra Anil K.,
Chandna Sudhir,
Saluja Daman,
Chopra Madhu
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201100593
Subject(s) - gastrin , cholecystokinin , antagonist , chemistry , fluorescence , receptor , cancer research , biophysics , microbiology and biotechnology , biochemistry , biology , secretion , physics , quantum mechanics
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 IC 50 of 4.79 n m, and the antagonist inhibited gastric acid secretion in an isolated lumen‐perfused mouse stomach assay (up to 51 % at 100 n m) . 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.