Synthesis of Small‐Molecule Fluorescent Probes for the In Vitro Imaging of Calcium‐Activated Potassium Channel K Ca 3.1
| Autor: | Marius Rieke, Zoltán Pethő, Sarah Maskri, Cristian A. Strassert, Christian Paul Konken, Oliver Koch, Iván Maisuls, Kathrin Brömmel, Bernhard Wünsch, Albrecht Schwab |
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| Rok vydání: | 2020 |
| Předmět: |
Boron Compounds
Molecular Dynamics Simulation 010402 general chemistry Ligands 01 natural sciences Catalysis chemistry.chemical_compound Humans Binding site Ion channel Research Articles cycloaddition non-small cell lung cancer Fluorescent Dyes Binding Sites Cycloaddition Reaction 010405 organic chemistry Chemistry General Chemistry General Medicine Intermediate-Conductance Calcium-Activated Potassium Channels Fluorescence Small molecule Calcium-activated potassium channel In vitro 0104 chemical sciences molecular modelling Microscopy Fluorescence A549 Cells Biophysics BODIPY Fluorescent Probes KCa3.1 channels Linker Immunostaining Research Article |
| Zdroj: | Angewandte Chemie (International Ed. in English) |
| ISSN: | 1521-3757 0044-8249 |
| DOI: | 10.1002/ange.202001201 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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