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

Ewa Szymanska; Darryl S Pickering; Birgitte Nielsen; Tommy N Johansen

doi:10.1016/j.bmc.2009.07.021

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

Ewa Szymanska, Darryl S Pickering, Birgitte Nielsen, Tommy N Johansen

13 Citations (Scopus)

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 language	English
Journal	Bioorganic & Medicinal Chemistry
Volume	17
Issue number	17
Pages (from-to)	6390-401
Number of pages	11
ISSN	0968-0896
DOIs	https://doi.org/10.1016/j.bmc.2009.07.021
Publication status	Published - 2009

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Former Faculty of Pharmaceutical Sciences

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10.1016/j.bmc.2009.07.021

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title = "3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands",

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.",

keywords = "Former Faculty of Pharmaceutical Sciences",

author = "Ewa Szymanska and Pickering, {Darryl S} and Birgitte Nielsen and Johansen, {Tommy N}",

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

year = "2009",

doi = "10.1016/j.bmc.2009.07.021",

language = "English",

volume = "17",

pages = "6390--401",

journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

publisher = "Pergamon Press",

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TY - JOUR

T1 - 3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands

AU - Szymanska, Ewa

AU - Pickering, Darryl S

AU - Nielsen, Birgitte

AU - Johansen, Tommy N

N1 - Keywords: Animals; Binding Sites; Computer Simulation; Ligands; Neurotransmitter Agents; Phenylalanine; Rats; Receptors, AMPA; Receptors, Kainic Acid; Recombinant Proteins

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.bmc.2009.07.021

DO - 10.1016/j.bmc.2009.07.021

M3 - Journal article

C2 - 19656686

SN - 0968-0896

VL - 17

SP - 6390

EP - 6401

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 17

ER -

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

Abstract

Keywords

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