Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid. / Frydenvang, Karla Andrea; Pickering, Darryl S; Greenwood, Jeremy R; Krogsgaard-Larsen, Niels; Brehm, Lotte; Nielsen, Birgitte; Vogensen, Stine Byskov; Hald, Helle; Kastrup, Jette Sandholm; Krogsgaard-Larsen, Povl; Clausen, Rasmus Prætorius.

In: Journal of Medicinal Chemistry, Vol. 53, No. 23, 10.11.2010, p. 8354-8361.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Frydenvang, KA, Pickering, DS, Greenwood, JR, Krogsgaard-Larsen, N, Brehm, L, Nielsen, B, Vogensen, SB, Hald, H, Kastrup, JS, Krogsgaard-Larsen, P & Clausen, RP 2010, 'Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid', Journal of Medicinal Chemistry, vol. 53, no. 23, pp. 8354-8361. https://doi.org/10.1021/jm101218a

APA

Frydenvang, K. A., Pickering, D. S., Greenwood, J. R., Krogsgaard-Larsen, N., Brehm, L., Nielsen, B., ... Clausen, R. P. (2010). Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid. Journal of Medicinal Chemistry, 53(23), 8354-8361. https://doi.org/10.1021/jm101218a

Vancouver

Frydenvang KA, Pickering DS, Greenwood JR, Krogsgaard-Larsen N, Brehm L, Nielsen B et al. Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid. Journal of Medicinal Chemistry. 2010 Nov 10;53(23):8354-8361. https://doi.org/10.1021/jm101218a

Author

Frydenvang, Karla Andrea ; Pickering, Darryl S ; Greenwood, Jeremy R ; Krogsgaard-Larsen, Niels ; Brehm, Lotte ; Nielsen, Birgitte ; Vogensen, Stine Byskov ; Hald, Helle ; Kastrup, Jette Sandholm ; Krogsgaard-Larsen, Povl ; Clausen, Rasmus Prætorius. / Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 23. pp. 8354-8361.

Bibtex

@article{a130e65c396148bbb7fdf4c0e30591f7,
title = "Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid",
abstract = "We describe an improved synthesis and detailed pharmacological characterization of the conformationally restricted analogue of the naturally occurring nonselective glutamate receptor agonist ibotenic acid (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA, 5) at AMPA receptor subtypes. Compound 5 was shown to be a subtype-discriminating agonist at AMPA receptors with higher binding affinity and functional potency at GluA1/2 compared to GluA3/4, unlike the isomeric analogue (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA, 4) that binds to all AMPA receptor subtypes with comparable potency. Biostructural X-ray crystallographic studies of 4 and 5 reveal different binding modes of (R)-4 and (S)-5 in the GluA2 agonist binding domain. WaterMap analysis of the GluA2 and GluA4 binding pockets with (R)-4 and (S)-5 suggests that the energy of hydration sites is ligand dependent, which may explain the observed selectivity.",
author = "Frydenvang, {Karla Andrea} and Pickering, {Darryl S} and Greenwood, {Jeremy R} and Niels Krogsgaard-Larsen and Lotte Brehm and Birgitte Nielsen and Vogensen, {Stine Byskov} and Helle Hald and Kastrup, {Jette Sandholm} and Povl Krogsgaard-Larsen and Clausen, {Rasmus Pr{\ae}torius}",
year = "2010",
month = "11",
day = "10",
doi = "10.1021/jm101218a",
language = "English",
volume = "53",
pages = "8354--8361",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

RIS

TY - JOUR

T1 - Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid

AU - Frydenvang, Karla Andrea

AU - Pickering, Darryl S

AU - Greenwood, Jeremy R

AU - Krogsgaard-Larsen, Niels

AU - Brehm, Lotte

AU - Nielsen, Birgitte

AU - Vogensen, Stine Byskov

AU - Hald, Helle

AU - Kastrup, Jette Sandholm

AU - Krogsgaard-Larsen, Povl

AU - Clausen, Rasmus Prætorius

PY - 2010/11/10

Y1 - 2010/11/10

N2 - We describe an improved synthesis and detailed pharmacological characterization of the conformationally restricted analogue of the naturally occurring nonselective glutamate receptor agonist ibotenic acid (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA, 5) at AMPA receptor subtypes. Compound 5 was shown to be a subtype-discriminating agonist at AMPA receptors with higher binding affinity and functional potency at GluA1/2 compared to GluA3/4, unlike the isomeric analogue (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA, 4) that binds to all AMPA receptor subtypes with comparable potency. Biostructural X-ray crystallographic studies of 4 and 5 reveal different binding modes of (R)-4 and (S)-5 in the GluA2 agonist binding domain. WaterMap analysis of the GluA2 and GluA4 binding pockets with (R)-4 and (S)-5 suggests that the energy of hydration sites is ligand dependent, which may explain the observed selectivity.

AB - We describe an improved synthesis and detailed pharmacological characterization of the conformationally restricted analogue of the naturally occurring nonselective glutamate receptor agonist ibotenic acid (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA, 5) at AMPA receptor subtypes. Compound 5 was shown to be a subtype-discriminating agonist at AMPA receptors with higher binding affinity and functional potency at GluA1/2 compared to GluA3/4, unlike the isomeric analogue (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA, 4) that binds to all AMPA receptor subtypes with comparable potency. Biostructural X-ray crystallographic studies of 4 and 5 reveal different binding modes of (R)-4 and (S)-5 in the GluA2 agonist binding domain. WaterMap analysis of the GluA2 and GluA4 binding pockets with (R)-4 and (S)-5 suggests that the energy of hydration sites is ligand dependent, which may explain the observed selectivity.

U2 - 10.1021/jm101218a

DO - 10.1021/jm101218a

M3 - Journal article

C2 - 21067182

VL - 53

SP - 8354

EP - 8361

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -

ID: 32258776