Rosier, Niklas and Moennich, Denise and Nagl, Martin and Schihada, Hannes and Sirbu, Alexei and Konar, Nergis and Reyes-Resina, Irene and Navarro, Gemma and Franco, Rafael and Kolb, Peter and Annibale, Paolo and Pockes, Steffen (2024) Shedding Light on the D1-Like Receptors: A Fluorescence-Based Toolbox for Visualization of the D1 and D5 Receptors. CHEMBIOCHEM, 25 (2). e202300658. ISSN 1439-4227, 1439-7633
Full text not available from this repository. (Request a copy)Abstract
Dopamine D-1-like receptors are the most abundant type of dopamine receptors in the central nervous system and, even after decades of discovery, still highly interesting for the study of neurological diseases. We herein describe the synthesis of a new set of fluorescent ligands, structurally derived from D1R antagonist SCH-23390 and labeled with two different fluorescent dyes, as tool compounds for the visualization of D-1-like receptors. Pharmacological characterization in radioligand binding studies identified UR-NR435 (25) as a high-affinity ligand for D-1-like receptors (pK(i) (D1R)=8.34, pK(i) (D5R)=7.62) with excellent selectivity towards D-2-like receptors. Compound 25 proved to be a neutral antagonist at the D1R and D5R in a G(s) heterotrimer dissociation assay, an important feature to avoid receptor internalization and degradation when working with whole cells. The neutral antagonist 25 displayed rapid association and complete dissociation to the D1R in kinetic binding studies using confocal microscopy verifying its applicability for fluorescence microscopy. Moreover, molecular brightness studies determined a single-digit nanomolar binding affinity of the ligand, which was in good agreement with radioligand binding data. For this reason, this fluorescent ligand is a useful tool for a sophisticated characterization of native D-1 receptors in a variety of experimental setups.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DOPAMINE D-1; LIGAND-BINDING; HISTAMINE H-3; HIGH-AFFINITY; PHARMACOLOGY; AGONIST; D1; BIOLUMINESCENCE; DIHYDREXIDINE; MODULATION; confocal microscopy; D-1-like receptors; dopamine receptors; fluorescent ligands; molecular brightness |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2024 07:53 |
| Last Modified: | 20 Mar 2024 07:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60224 |
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