Tritium and deuterium labelling of a kainate receptor antagonist and evaluation as a radioligand
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
2020/39/B/NZ7/00558
National Science Centre Poland
61388963
Academy of Sciences of the Czech Republic
PubMed
38332677
DOI
10.1002/jlcr.4087
Knihovny.cz E-zdroje
- Klíčová slova
- ionotropic glutamate receptors, quinoxaline‐2,3‐diones, tritium labelling,
- MeSH
- AMPA receptory chemie metabolismus MeSH
- deuterium MeSH
- HEK293 buňky MeSH
- krysa rodu Rattus MeSH
- kyselina glutamová * MeSH
- lidé MeSH
- receptory kyseliny kainové * chemie metabolismus MeSH
- tritium MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- AMPA receptory MeSH
- deuterium MeSH
- kyselina glutamová * MeSH
- receptory kyseliny kainové * MeSH
- tritium MeSH
Kainate receptors play a crucial role in mediating synaptic transmission within the central nervous system. However, the lack of selective pharmacological tool compounds for the GluK3 subunit represents a significant challenge in studying these receptors. Recently presented compound 1 stands out as a potent antagonist of GluK3 receptors, exhibiting nanomolar affinity at GluK3 receptors and strongly inhibiting glutamate-induced currents at homomeric GluK1 and GluK3 receptors in HEK293 cells with Kb values of 65 and 39 nM, respectively. This study presents the synthesis of two potent GluK3-preferring iodine derivatives of compound 1, serving as precursors for radiolabelling. Furthermore, we demonstrate the optimisation of dehalogenation conditions using hydrogen and deuterium, resulting in [2H]-1, and demonstrate the efficient synthesis of the radioligand [3H]-1 with a specific activity of 1.48 TBq/mmol (40.1 Ci/mmol). Radioligand binding studies conducted with [3H]-1 as a radiotracer at GluK1, GluK2, and GluK3 receptors expressed in Sf9 and rat P2 membranes demonstrated its potential applicability for selectively studying native GluK3 receptors in the presence of GluK1 and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-blocking ligands.
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