Fluorescent Tools for the Imaging of Dopamine D2 -Like Receptors.
Chembiochem
; 25(2): e202300659, 2024 01 15.
Article
em En
| MEDLINE
| ID: mdl-37942961
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dopamina
/
Receptores de Dopamina D2
Idioma:
En
Revista:
Chembiochem
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha