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

Autor: Borgarelli C; Sustainable Chemistry for Metals and Molecules (SCM2), Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Box 2404, 3001 Leuven, Belgium., Klingl YE; Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, 3000 Leuven, Belgium.; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, 3000 Leuven, Belgium., Escamilla-Ayala A; Center for Brain & Disease Research, & VIB BioImaging Core, VIB-KU Leuven Campus Gasthuisberg O&N5, box 602 Herestraat 49, 3000 Leuven, Belgium.; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Campus Gasthuisberg O&N5-box 602 Herestraat 49, 3000 Leuven, Belgium., Scarponi C; CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) Paseo Miramon, 20014 San Sebastian, Guipuzcoa, Spain., La Rovere RML; Dep. Cellular & Molecular Medicine, KU Leuven, Lab. Molecular & Cellular Signaling, Campus Gasthuisberg O/N-1 bus 802, Herestraat 49, 3000 Leuven, Belgium., Stoklund Dittlau K; Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, 3000 Leuven, Belgium.; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, 3000 Leuven, Belgium., Bultynck G; Dep. Cellular & Molecular Medicine, KU Leuven, Lab. Molecular & Cellular Signaling, Campus Gasthuisberg O/N-1 bus 802, Herestraat 49, 3000 Leuven, Belgium., Sampaolesi M; Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Schoenberger M; Department for Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium., Munck S; Center for Brain & Disease Research, & VIB BioImaging Core, VIB-KU Leuven Campus Gasthuisberg O&N5, box 602 Herestraat 49, 3000 Leuven, Belgium.; Department of Neurosciences, Leuven Brain Institute, KU Leuven, Campus Gasthuisberg O&N5-box 602 Herestraat 49, 3000 Leuven, Belgium., Van Den Bosch L; Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, 3000 Leuven, Belgium.; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, 3000 Leuven, Belgium., De Borggraeve WM; Sustainable Chemistry for Metals and Molecules (SCM2), Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Box 2404, 3001 Leuven, Belgium., Ismalaj E; Sustainable Chemistry for Metals and Molecules (SCM2), Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Box 2404, 3001 Leuven, Belgium.; CIC biomaGUNE, Basque Research and Technology Alliance (BRTA) Paseo Miramon, 20014 San Sebastian, Guipuzcoa, Spain.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2024 Oct 24; Vol. 67 (20), pp. 18038-18052. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1021/acs.jmedchem.4c00565
Abstrakt: 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 Ca 2+ 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.
Databáze: MEDLINE