3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands

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    Abstract

    On the basis of X-ray structures of ionotropic glutamate receptor constructs in complex with amino acid-based AMPA and kainate receptor antagonists, a series of rigid as well as flexible biaromatic alanine derivatives carrying selected hydrogen bond acceptors and donors have been synthesized in order to investigate the structural determinants for receptor selectivity between AMPA and the GluR5 subtype of kainate receptors. Compounds selective for either GluR5 or AMPA receptors were identified. One particular substituent position appeared to be of special importance for control of ligand selectivity. Using molecular modeling the observed structure-activity relationships at AMPA and GluR5 receptors were deduced.
    Original languageEnglish
    JournalBioorganic & Medicinal Chemistry
    Volume17
    Issue number17
    Pages (from-to)6390-401
    Number of pages11
    ISSN0968-0896
    DOIs
    Publication statusPublished - 2009

    Bibliographical note

    Keywords: Animals; Binding Sites; Computer Simulation; Ligands; Neurotransmitter Agents; Phenylalanine; Rats; Receptors, AMPA; Receptors, Kainic Acid; Recombinant Proteins

    Keywords

    • Former Faculty of Pharmaceutical Sciences

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