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Nagl, Martin ; Moennich, Denise ; Rosier, Niklas ; Schihada, Hannes ; Sirbu, Alexei ; Konar, Nergis ; Reyes-Resina, Irene ; Navarro, Gemma ; Franco, Rafael ; Kolb, Peter ; Annibale, Paolo ; Pockes, Steffen

Fluorescent Tools for the Imaging of Dopamine D2‐Like Receptors

Nagl, Martin, Moennich, Denise, Rosier, Niklas , Schihada, Hannes, Sirbu, Alexei, Konar, Nergis, Reyes-Resina, Irene, Navarro, Gemma, Franco, Rafael, Kolb, Peter, Annibale, Paolo und Pockes, Steffen (2023) Fluorescent Tools for the Imaging of Dopamine D2‐Like Receptors. ChemBioChem.

Veröffentlichungsdatum dieses Volltextes: 22 Nov 2023 08:50
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.55058


Zusammenfassung

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) ...

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 (D2longR)=8.24, pKi (D3R)=8.58, pKi (D4R)=7.78) with decent selectivity towards D1-like receptors. Compound 20 is a neutral antagonist in a Go1 activation assay at the D2longR, D3R, and D4R, 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 D2longR 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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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftChemBioChem
Verlag:Wiley
Datum9 November 2023
InstitutionenChemie und Pharmazie > Institut für Pharmazie > Lehrstuhl Pharmazeutische / Medizinische Chemie I (Prof. Elz)
Identifikationsnummer
WertTyp
10.1002/cbic.202300659DOI
Stichwörter / Keywordsconfocal microscopy · D2-like receptors · dopamine receptors · fluorescent ligands · molecular brightness
Dewey-Dezimal-Klassifikation500 Naturwissenschaften und Mathematik > 540 Chemie
600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenZum Teil
URN der UB Regensburgurn:nbn:de:bvb:355-epub-550586
Dokumenten-ID55058

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