Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency

Research output: Contribution to journalJournal articlepeer-review

Standard

Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency. / Beich-Frandsen, Mads; Pickering, Darryl S; Mirza, Osman; Johansen, Tommy N; Greenwood, Jeremy; Vestergaard, Bente; Schousboe, Arne; Gajhede, Michael; Liljefors, Tommy; Kastrup, Jette S.

In: Journal of Medicinal Chemistry, Vol. 51, No. 5, 2008, p. 1459-63.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Beich-Frandsen, M, Pickering, DS, Mirza, O, Johansen, TN, Greenwood, J, Vestergaard, B, Schousboe, A, Gajhede, M, Liljefors, T & Kastrup, JS 2008, 'Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency', Journal of Medicinal Chemistry, vol. 51, no. 5, pp. 1459-63. https://doi.org/10.1021/jm701126w

APA

Beich-Frandsen, M., Pickering, D. S., Mirza, O., Johansen, T. N., Greenwood, J., Vestergaard, B., Schousboe, A., Gajhede, M., Liljefors, T., & Kastrup, J. S. (2008). Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency. Journal of Medicinal Chemistry, 51(5), 1459-63. https://doi.org/10.1021/jm701126w

Vancouver

Beich-Frandsen M, Pickering DS, Mirza O, Johansen TN, Greenwood J, Vestergaard B et al. Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency. Journal of Medicinal Chemistry. 2008;51(5):1459-63. https://doi.org/10.1021/jm701126w

Author

Beich-Frandsen, Mads ; Pickering, Darryl S ; Mirza, Osman ; Johansen, Tommy N ; Greenwood, Jeremy ; Vestergaard, Bente ; Schousboe, Arne ; Gajhede, Michael ; Liljefors, Tommy ; Kastrup, Jette S. / Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 5. pp. 1459-63.

Bibtex

@article{c86905e0a04011dd86a6000ea68e967b,
title = "Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency",
abstract = "AMPA-type ionotropic glutamate receptors generally display high stereoselectivity in agonist binding. However, the stereoisomers of 2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid (TDPA) have similar enantiopharmacology. To understand this observation, we have determined the X-ray structures of ( R)-TDPA and ( S)-TDPA in complex with the ligand-binding core of iGluR2 and investigated the binding pharmacology at AMPA and kainate receptors. Both enantiomers induce full domain closure in iGluR2 but adopt different conformations when binding to the receptor, which may explain the similar enantiopharmacology.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Mads Beich-Frandsen and Pickering, {Darryl S} and Osman Mirza and Johansen, {Tommy N} and Jeremy Greenwood and Bente Vestergaard and Arne Schousboe and Michael Gajhede and Tommy Liljefors and Kastrup, {Jette S}",
note = "Keywords: Alanine; Binding Sites; Crystallography, X-Ray; Ligands; Models, Molecular; Radioligand Assay; Receptors, AMPA; Recombinant Proteins; Stereoisomerism; Structure-Activity Relationship; Thiadiazoles",
year = "2008",
doi = "10.1021/jm701126w",
language = "English",
volume = "51",
pages = "1459--63",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "5",

}

RIS

TY - JOUR

T1 - Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency

AU - Beich-Frandsen, Mads

AU - Pickering, Darryl S

AU - Mirza, Osman

AU - Johansen, Tommy N

AU - Greenwood, Jeremy

AU - Vestergaard, Bente

AU - Schousboe, Arne

AU - Gajhede, Michael

AU - Liljefors, Tommy

AU - Kastrup, Jette S

N1 - Keywords: Alanine; Binding Sites; Crystallography, X-Ray; Ligands; Models, Molecular; Radioligand Assay; Receptors, AMPA; Recombinant Proteins; Stereoisomerism; Structure-Activity Relationship; Thiadiazoles

PY - 2008

Y1 - 2008

N2 - AMPA-type ionotropic glutamate receptors generally display high stereoselectivity in agonist binding. However, the stereoisomers of 2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid (TDPA) have similar enantiopharmacology. To understand this observation, we have determined the X-ray structures of ( R)-TDPA and ( S)-TDPA in complex with the ligand-binding core of iGluR2 and investigated the binding pharmacology at AMPA and kainate receptors. Both enantiomers induce full domain closure in iGluR2 but adopt different conformations when binding to the receptor, which may explain the similar enantiopharmacology.

AB - AMPA-type ionotropic glutamate receptors generally display high stereoselectivity in agonist binding. However, the stereoisomers of 2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid (TDPA) have similar enantiopharmacology. To understand this observation, we have determined the X-ray structures of ( R)-TDPA and ( S)-TDPA in complex with the ligand-binding core of iGluR2 and investigated the binding pharmacology at AMPA and kainate receptors. Both enantiomers induce full domain closure in iGluR2 but adopt different conformations when binding to the receptor, which may explain the similar enantiopharmacology.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jm701126w

DO - 10.1021/jm701126w

M3 - Journal article

C2 - 18269227

VL - 51

SP - 1459

EP - 1463

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 5

ER -

ID: 6747651