Synthesis of Small‐Molecule Fluorescent Probes for the In Vitro Imaging of Calcium‐Activated Potassium Channel KCa3.1

Small‐molecule probes for the in vitro imaging of KCa3.1 channel‐expressing cells were developed. Senicapoc, showing high affinity and selectivity for the KCa3.1 channels, was chosen as the targeting component. BODIPY dyes 15–20 were synthesized and connected by a CuI‐catalyzed azide–alkyne [3+2]cyc...

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Veröffentlicht in:Angewandte Chemie International Edition 2020-05, Vol.59 (21), p.8277-8284
Hauptverfasser: Brömmel, Kathrin, Maskri, Sarah, Maisuls, Ivan, Konken, Christian Paul, Rieke, Marius, Pethő, Zoltan, Strassert, Cristian A., Koch, Oliver, Schwab, Albrecht, Wünsch, Bernhard
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Sprache:eng
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Zusammenfassung:Small‐molecule probes for the in vitro imaging of KCa3.1 channel‐expressing cells were developed. Senicapoc, showing high affinity and selectivity for the KCa3.1 channels, was chosen as the targeting component. BODIPY dyes 15–20 were synthesized and connected by a CuI‐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 KCa3.1 channels in NSCLC cells. The specificity was shown by removing the punctate staining pattern by pre‐incubation with senicapoc. The density of KCa3.1 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. Imaging channels: Small‐molecule probes for the in vitro imaging of KCa3.1 channel‐expressing cells were designed and developed. Using senicapoc as the targeting component, the BODIPY‐labeled probes could selectively stain the channels in living cells and the channel punctate structure could be observed.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202001201