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.
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 aC u I -catalyzed azidealkyne [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.T he specificity was shown by removing the punctate staining pattern by preincubation with senicapoc.T he 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.M olecular 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.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.
Expression of the Ca2+ activated potassium channel 3.1 (KCa3.1) channel (also known as the Gàrdos channel) is dysregulated in many tumor entities and has predictive power with respect to patient survival.
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