Synthesis and receptor binding affinity of new selective GluR5 ligands

Research output: Contribution to journalJournal articlepeer-review

Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropic glutamic acid receptors. The (S)-enantiomers of E-4-(2,2-dimethylpropylidene)glutamic acid ((S)-1) and E-4-(3,3-dimethylbutylidene)glutamic acid ((S)-2) were shown to be selective and high affinity GluR5 ligands, with Ki values of 0.024 and 0.39 microM, respectively, compared to Ki values at GluR2 of 3.0 and 2.0 microM. respectively. Their affinities in the [3H]AMPA binding assay on native cortical receptors were shown to correlate with their GluR2 affinity rather than their GluR5 affinity. No affinity for GluR6 was detected (IC50 > 100 microM).
Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Issue number4
Pages (from-to)875-9
Publication statusPublished - Apr 2001

    Research areas

  • Cell Line, Chromatography, High Pressure Liquid, Glutamates, Humans, Indicators and Reagents, Ligands, Magnetic Resonance Spectroscopy, Receptors, AMPA, Receptors, Kainic Acid, Tumor Cells, Cultured

ID: 45613875