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Synthesis of Small‐Molecule Fluorescent Probes for the In Vitro Imaging of Calcium‐Activated Potassium Channel K Ca 3.1
Author(s) -
Brömmel Kathrin,
Maskri Sarah,
Maisuls Ivan,
Konken Christian Paul,
Rieke Marius,
Pethő Zoltan,
Strassert Cristian A.,
Koch Oliver,
Schwab Albrecht,
Wünsch Bernhard
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202001201
Subject(s) - chemistry , fluorescence , in vitro , biophysics , linker , potassium channel , molecule , small molecule , staining , immunostaining , biochemistry , medicine , physics , immunohistochemistry , organic chemistry , pathology , quantum mechanics , computer science , biology , operating system
Abstract Small‐molecule probes for the in vitro imaging of K Ca 3.1 channel‐expressing cells were developed. Senicapoc, showing high affinity and selectivity for the K Ca 3.1 channels, was chosen as the targeting component. BODIPY dyes 15 – 20 were synthesized and connected by a Cu I ‐catalyzed azide–alkyne [3+2]cycloaddition with propargyl ether senicapoc derivative 8 , yielding fluorescently labeled ligands 21 – 26 . The dimethylpyrrole‐based imaging probes 25 and 26 allow staining of K Ca 3.1 channels in NSCLC cells. The specificity was shown by removing the punctate staining pattern by pre‐incubation with senicapoc. The density of K Ca 3.1 channels detected with 25 and by immunostaining was identical. The punctate structure of the labeled channels could also be observed in living cells. Molecular modeling showed binding of the senicapoc‐targeting component towards the binding site within the ion channel and orientation of the linker with the dye along the inner surface of the ion channel.