Novel Far-Red Fluorescent 1,4-Dihydropyridines for L‑Type Calcium Channel Imaging

Upregulation of L-type calcium channels (LTCCs) is implicated in a range of cardiovascular and neurological disorders. Therefore, the development of toolboxes that unlock fast imaging protocols in live cells is coveted. Herein, we report a library of first-in-class far-red small-molecule-based fluor...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2024-10, Vol.67 (20), p.18038-18052
Main Authors: Borgarelli, Carlotta, Klingl, Yvonne E., Escamilla-Ayala, Abril, Scarponi, Carlotta, La Rovere, Rita M. L., Stoklund Dittlau, Katarina, Bultynck, Geert, Sampaolesi, Maurilio, Schoenberger, Matthias, Munck, Sebastian, Van Den Bosch, Ludo, De Borggraeve, Wim M., Ismalaj, Ermal
Format: Article
Language:English
Subjects:
Calcium - metabolism
Calcium Channels, L-Type - metabolism
Dihydropyridines - chemical synthesis
Dihydropyridines - chemistry
Dihydropyridines - pharmacology
Fluorescent Dyes - chemical synthesis
Fluorescent Dyes - chemistry
HEK293 Cells
Humans
Optical Imaging
Patch-Clamp Techniques
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Upregulation of L-type calcium channels (LTCCs) is implicated in a range of cardiovascular and neurological disorders. Therefore, the development of toolboxes that unlock fast imaging protocols in live cells is coveted. Herein, we report a library of first-in-class far-red small-molecule-based fluorescent ligands (FluoDiPines), able to target LTCCs. All fluorescent ligands were evaluated in whole-cell patch-clamp and live-cell Ca2+ imaging whereby FluoDiPine 6 was found to be the best candidate for live-cell fluorescence imaging. Low concentration of FluoDiPine 6 (50 nM) and a quick labeling protocol (5 min) are successfully applied to fixed and live cells to image LTCCs with good specificity.
ISSN:0022-2623
1520-4804
1520-4804
DOI:10.1021/acs.jmedchem.4c00565