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 fluorescent ligands (FluoDiPines), able to target LTCCs. All fluorescent ligands were evaluated in whole-cell patch-clamp and live-cell Ca<sup>2+</sup> imaging whereby <b>FluoDiPine 6</b> was found to be the best candidate for live-cell fluorescence imaging. Low concentration of <b>FluoDiPine 6</b> (50 nM) and a quick labeling protocol (5 min) are successfully applied to fixed and live cells to image LTCCs with good specificity.
Authors
- Yvonne E. Klingl (ORCID: https://orcid.org/0000-0003-2779-3357)
- Matthias Schoenberger
- Geert Bultynck (ORCID: https://orcid.org/0000-0002-5968-4828)
- Abril Escamilla‐Ayala (ORCID: https://orcid.org/0000-0002-5761-0999)
- Rita Maria Laura La Rovere (ORCID: https://orcid.org/0000-0002-6543-9829)
- Carlotta Borgarelli (ORCID: https://orcid.org/0000-0002-9632-2906)
- Wim M. De Borggraeve (ORCID: https://orcid.org/0000-0001-7813-6192)
- Ermal Ismalaj (ORCID: https://orcid.org/0000-0003-2015-2303)
- Ludo Van Den Bosch (ORCID: https://orcid.org/0000-0003-0104-4067)
- Sebastian Munck (ORCID: https://orcid.org/0000-0002-5182-5358)
- Maurilio Sampaolesi (ORCID: https://orcid.org/0000-0002-2422-3757)
- Katarina Stoklund Dittlau (ORCID: https://orcid.org/0000-0003-2776-2892)
- C. Scarponi
Institutions
- CIC biomaGUNE (ES)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- KU Leuven (BE)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2024-10-10
- DOI
- https://doi.org/10.1021/acs.jmedchem.4c00565
- Citations
- 1
- Primary Topic
- Pharmacological Receptor Mechanisms and Effects
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- Fonds Wetenschappelijk Onderzoek
- Ministero della Salute
- KU Leuven
- Onderzoeksraad, KU Leuven
- Vlaamse regering
- Herculesstichting
- Diputación Foral de Gipuzkoa
- Interreg