Tweaking subtype-selectivity and agonist efficacy at (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in a small series of BnTetAMPA analogues

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Tweaking subtype-selectivity and agonist efficacy at (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in a small series of BnTetAMPA analogues. / Wang, Shuang-Yan; Larsen, Younes; Navarrete, Cristina V.; Jensen, Anders A.; Nielsen, Birgitte; Al-Musaed, Ali; Frydenvang, Karla; Kastrup, Jette Sandholm; Pickering, Darryl S; Clausen, Rasmus Prætorius.

In: Journal of Medicinal Chemistry, Vol. 59, No. 5, 2016, p. 2244-2254.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Wang, S-Y, Larsen, Y, Navarrete, CV, Jensen, AA, Nielsen, B, Al-Musaed, A, Frydenvang, K, Kastrup, JS, Pickering, DS & Clausen, RP 2016, 'Tweaking subtype-selectivity and agonist efficacy at (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in a small series of BnTetAMPA analogues', Journal of Medicinal Chemistry, vol. 59, no. 5, pp. 2244-2254. https://doi.org/10.1021/acs.jmedchem.5b01982

APA

Wang, S-Y., Larsen, Y., Navarrete, C. V., Jensen, A. A., Nielsen, B., Al-Musaed, A., Frydenvang, K., Kastrup, J. S., Pickering, D. S., & Clausen, R. P. (2016). Tweaking subtype-selectivity and agonist efficacy at (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in a small series of BnTetAMPA analogues. Journal of Medicinal Chemistry, 59(5), 2244-2254. https://doi.org/10.1021/acs.jmedchem.5b01982

Vancouver

Wang S-Y, Larsen Y, Navarrete CV, Jensen AA, Nielsen B, Al-Musaed A et al. Tweaking subtype-selectivity and agonist efficacy at (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in a small series of BnTetAMPA analogues. Journal of Medicinal Chemistry. 2016;59(5):2244-2254. https://doi.org/10.1021/acs.jmedchem.5b01982

Author

Wang, Shuang-Yan ; Larsen, Younes ; Navarrete, Cristina V. ; Jensen, Anders A. ; Nielsen, Birgitte ; Al-Musaed, Ali ; Frydenvang, Karla ; Kastrup, Jette Sandholm ; Pickering, Darryl S ; Clausen, Rasmus Prætorius. / Tweaking subtype-selectivity and agonist efficacy at (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in a small series of BnTetAMPA analogues. In: Journal of Medicinal Chemistry. 2016 ; Vol. 59, No. 5. pp. 2244-2254.

Bibtex

@article{e4b4c109daae41d7a905e687c449e919,
title = "Tweaking subtype-selectivity and agonist efficacy at (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in a small series of BnTetAMPA analogues",
abstract = "A series of analogues of the (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptor agonist BnTetAMPA (5b) were synthesized and characterized pharmacologically in radioligand binding assays at native and cloned AMPA receptors and functionally by two-electrode voltage clamp electrophysiology at the four homomeric AMPA receptors expressed in Xenopus laevis oocytes. The analogues 6 and 7 exhibit very different pharmacological profiles with binding affinity preference for the subtypes GluA1 and GluA3, respectively. X-ray crystal structures of three ligands (6, 7, and 8) in complex with the agonist binding domain (ABD) of GluA2 show that they induce full domain closure despite their low agonist efficacies. Trp767 in GluA2 ABD could be an important determinant for partial agonism of this compound series at AMPA receptors, since agonist efficacy also correlated with the location of the Trp767 side chain.",
author = "Shuang-Yan Wang and Younes Larsen and Navarrete, {Cristina V.} and Jensen, {Anders A.} and Birgitte Nielsen and Ali Al-Musaed and Karla Frydenvang and Kastrup, {Jette Sandholm} and Pickering, {Darryl S} and Clausen, {Rasmus Pr{\ae}torius}",
year = "2016",
doi = "10.1021/acs.jmedchem.5b01982",
language = "English",
volume = "59",
pages = "2244--2254",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "5",

}

RIS

TY - JOUR

T1 - Tweaking subtype-selectivity and agonist efficacy at (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in a small series of BnTetAMPA analogues

AU - Wang, Shuang-Yan

AU - Larsen, Younes

AU - Navarrete, Cristina V.

AU - Jensen, Anders A.

AU - Nielsen, Birgitte

AU - Al-Musaed, Ali

AU - Frydenvang, Karla

AU - Kastrup, Jette Sandholm

AU - Pickering, Darryl S

AU - Clausen, Rasmus Prætorius

PY - 2016

Y1 - 2016

N2 - A series of analogues of the (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptor agonist BnTetAMPA (5b) were synthesized and characterized pharmacologically in radioligand binding assays at native and cloned AMPA receptors and functionally by two-electrode voltage clamp electrophysiology at the four homomeric AMPA receptors expressed in Xenopus laevis oocytes. The analogues 6 and 7 exhibit very different pharmacological profiles with binding affinity preference for the subtypes GluA1 and GluA3, respectively. X-ray crystal structures of three ligands (6, 7, and 8) in complex with the agonist binding domain (ABD) of GluA2 show that they induce full domain closure despite their low agonist efficacies. Trp767 in GluA2 ABD could be an important determinant for partial agonism of this compound series at AMPA receptors, since agonist efficacy also correlated with the location of the Trp767 side chain.

AB - A series of analogues of the (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptor agonist BnTetAMPA (5b) were synthesized and characterized pharmacologically in radioligand binding assays at native and cloned AMPA receptors and functionally by two-electrode voltage clamp electrophysiology at the four homomeric AMPA receptors expressed in Xenopus laevis oocytes. The analogues 6 and 7 exhibit very different pharmacological profiles with binding affinity preference for the subtypes GluA1 and GluA3, respectively. X-ray crystal structures of three ligands (6, 7, and 8) in complex with the agonist binding domain (ABD) of GluA2 show that they induce full domain closure despite their low agonist efficacies. Trp767 in GluA2 ABD could be an important determinant for partial agonism of this compound series at AMPA receptors, since agonist efficacy also correlated with the location of the Trp767 side chain.

U2 - 10.1021/acs.jmedchem.5b01982

DO - 10.1021/acs.jmedchem.5b01982

M3 - Journal article

C2 - 26862980

VL - 59

SP - 2244

EP - 2254

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 5

ER -

ID: 154014642