17/01/2025

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

Title: Novel Far-Red Fluorescent 1,4-Dihydropyridines for L-Type Calcium Channel Imaging
Authors:

Borgarelli, C; Klingl, YE; Escamilla-Ayala, A; Scarponi, C; La Rovere, RML; Dittlau, KS; Bultynck, G; Sampaolesi, M; Schoenberger, M; Munck, S; Van Den Bosch, L; De Borggraeve, WM; Ismalaj, E

Journal: J. Med. Chem. 2024. DOI: 10.1021/acs.jmedchem.4c00565

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.

DOI: 10.1021/acs.jmedchem.4c00565