Fluorescent Tools for the Imaging of Dopamine D2 -Like Receptors
© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH..
The family of dopamine D2 -like receptors represents an interesting target for a variety of neurological diseases, e. g. Parkinson's disease (PD), addiction, or schizophrenia. In this study we describe the synthesis of a new set of fluorescent ligands as tools for visualization of dopamine D2 -like receptors. Pharmacological characterization in radioligand binding studies identified UR-MN212 (20) as a high-affinity ligand for D2 -like receptors (pKi (D2long R)=8.24, pKi (D3 R)=8.58, pKi (D4 R)=7.78) with decent selectivity towards D1 -like receptors. Compound 20 is a neutral antagonist in a Go1 activation assay at the D2long R, D3 R, and D4 R, which is an important feature for studies using whole cells. The neutral antagonist 20, equipped with a 5-TAMRA dye, displayed rapid association to the D2long R in binding studies using confocal microscopy demonstrating its suitability for fluorescence microscopy. Furthermore, in molecular brightness studies, the ligand's binding affinity could be determined in a single-digit nanomolar range that was in good agreement with radioligand binding data. Therefore, the fluorescent compound can be used for quantitative characterization of native D2 -like receptors in a broad variety of experimental setups.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Chembiochem : a European journal of chemical biology - 25(2024), 2 vom: 15. Jan., Seite e202300659 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nagl, Martin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.01.2024 Date Revised 26.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cbic.202300659 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The family of dopamine D2 -like receptors represents an interesting target for a variety of neurological diseases, e. g. Parkinson's disease (PD), addiction, or schizophrenia. In this study we describe the synthesis of a new set of fluorescent ligands as tools for visualization of dopamine D2 -like receptors. Pharmacological characterization in radioligand binding studies identified UR-MN212 (20) as a high-affinity ligand for D2 -like receptors (pKi (D2long R)=8.24, pKi (D3 R)=8.58, pKi (D4 R)=7.78) with decent selectivity towards D1 -like receptors. Compound 20 is a neutral antagonist in a Go1 activation assay at the D2long R, D3 R, and D4 R, which is an important feature for studies using whole cells. The neutral antagonist 20, equipped with a 5-TAMRA dye, displayed rapid association to the D2long R in binding studies using confocal microscopy demonstrating its suitability for fluorescence microscopy. Furthermore, in molecular brightness studies, the ligand's binding affinity could be determined in a single-digit nanomolar range that was in good agreement with radioligand binding data. Therefore, the fluorescent compound can be used for quantitative characterization of native D2 -like receptors in a broad variety of experimental setups | ||
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| 700 | 1 | |a Rosier, Niklas |e verfasserin |4 aut | |
| 700 | 1 | |a Schihada, Hannes |e verfasserin |4 aut | |
| 700 | 1 | |a Sirbu, Alexei |e verfasserin |4 aut | |
| 700 | 1 | |a Konar, Nergis |e verfasserin |4 aut | |
| 700 | 1 | |a Reyes-Resina, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Navarro, Gemma |e verfasserin |4 aut | |
| 700 | 1 | |a Franco, Rafael |e verfasserin |4 aut | |
| 700 | 1 | |a Kolb, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Annibale, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Pockes, Steffen |e verfasserin |4 aut | |
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