Open AccessFluorescent H2 Receptor Squaramide-Type Antagonists: Synthesis, Characterization, and Applications
Author(s) -
Sabrina Biselli,
Inês S. Alencastre,
Katharina Tropmann,
Daniela Erdmann,
Mengya Chen,
Timo Littmann,
André F. Maia,
María Gómez-Lázaro,
Miho Tanaka,
Toshio Ozawa,
Max Keller,
Meriem Lamghari,
Armin Buschauer,
Günther Bernhardt
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00033
Subject(s) - fluorescence , cyanine , pyridinium , chemistry , binding affinities , confocal microscopy , ligand (biochemistry) , affinities , combinatorial chemistry , biophysics , fluorescence microscope , squaramide , receptor , flow cytometry , binding site , radioligand assay , receptor–ligand kinetics , stereochemistry , biochemistry , biology , microbiology and biotechnology , organic chemistry , physics , quantum mechanics , enantioselective synthesis , organocatalysis , catalysis
Fluorescence labeled ligands have been gaining importance as molecular tools, enabling receptor-ligand-binding studies by various fluorescence-based techniques. Aiming at red-emitting fluorescent ligands for the hH 2 R, a series of squaramides labeled with pyridinium or cyanine fluorophores ( 19 - 27 ) was synthesized and characterized. The highest hH 2 R affinities in radioligand competition binding assays were obtained in the case of pyridinium labeled antagonists 19 - 21 (p K i : 7.71-7.76) and cyanine labeled antagonists 23 and 25 (p K i : 7.67, 7.11). These fluorescent ligands proved to be useful tools for binding studies (saturation and competition binding as well as kinetic experiments), using confocal microscopy, flow cytometry, and high content imaging. Saturation binding experiments revealed p K d values comparable to the p K i values. The fluorescent probes 21 , 23 , and 25 could be used to localize H 2 receptors in HEK cells and to determine the binding affinities of unlabeled compounds.