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

Research output: Contribution to journalJournal articleResearchpeer-review

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
Issue number17
Pages (from-to)6390-401
Number of pages11
Publication statusPublished - 2009

Bibliographical note

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

ID: 17084258