Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid. / Larsen, Ann Møller; Venskutonyte, Raminta; Valadés, Elena Antón; Nielsen, Birgitte; Pickering, Darryl S; Bunch, Lennart.

In: ACS Chemical Neuroscience, Vol. 2, No. 2, 04.11.2011, p. 107-114.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Larsen, AM, Venskutonyte, R, Valadés, EA, Nielsen, B, Pickering, DS & Bunch, L 2011, 'Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid', ACS Chemical Neuroscience, vol. 2, no. 2, pp. 107-114. https://doi.org/10.1021/cn100093f

APA

Larsen, A. M., Venskutonyte, R., Valadés, E. A., Nielsen, B., Pickering, D. S., & Bunch, L. (2011). Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid. ACS Chemical Neuroscience, 2(2), 107-114. https://doi.org/10.1021/cn100093f

Vancouver

Larsen AM, Venskutonyte R, Valadés EA, Nielsen B, Pickering DS, Bunch L. Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid. ACS Chemical Neuroscience. 2011 Nov 4;2(2):107-114. https://doi.org/10.1021/cn100093f

Author

Larsen, Ann Møller ; Venskutonyte, Raminta ; Valadés, Elena Antón ; Nielsen, Birgitte ; Pickering, Darryl S ; Bunch, Lennart. / Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid. In: ACS Chemical Neuroscience. 2011 ; Vol. 2, No. 2. pp. 107-114.

Bibtex

@article{95c6aebd0c3745e682bff1d652f39e98,
title = "Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid",
abstract = "The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/ or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, we present the discovery of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid (1) based on a rational design process. Target compound 1 was synthesized by a stereoselective strategy in 10 steps from commercially available starting materials. Binding affinities of 1 at native ionotropic Glu receptors were determined to be in the micromolar range (AMPA, 51 µM; KA, 22 µM; NMDA 6 µM), with the highest affinity for cloned homomeric KA receptor subtypes GluK1,3 (3.0 and 8.1 µM, respectively). Functional characterization of 1 by two electrode voltage clamp (TEVC) electrophysiology at a nondesensitizing mutant of GluK1 showed full competitive antagonistic behavior with a Kb of 11.4 µM.",
author = "Larsen, {Ann M{\o}ller} and Raminta Venskutonyte and Valad{\'e}s, {Elena Ant{\'o}n} and Birgitte Nielsen and Pickering, {Darryl S} and Lennart Bunch",
year = "2011",
month = "11",
day = "4",
doi = "10.1021/cn100093f",
language = "English",
volume = "2",
pages = "107--114",
journal = "A C S Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "2",

}

RIS

TY - JOUR

T1 - Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid

AU - Larsen, Ann Møller

AU - Venskutonyte, Raminta

AU - Valadés, Elena Antón

AU - Nielsen, Birgitte

AU - Pickering, Darryl S

AU - Bunch, Lennart

PY - 2011/11/4

Y1 - 2011/11/4

N2 - The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/ or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, we present the discovery of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid (1) based on a rational design process. Target compound 1 was synthesized by a stereoselective strategy in 10 steps from commercially available starting materials. Binding affinities of 1 at native ionotropic Glu receptors were determined to be in the micromolar range (AMPA, 51 µM; KA, 22 µM; NMDA 6 µM), with the highest affinity for cloned homomeric KA receptor subtypes GluK1,3 (3.0 and 8.1 µM, respectively). Functional characterization of 1 by two electrode voltage clamp (TEVC) electrophysiology at a nondesensitizing mutant of GluK1 showed full competitive antagonistic behavior with a Kb of 11.4 µM.

AB - The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/ or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, we present the discovery of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid (1) based on a rational design process. Target compound 1 was synthesized by a stereoselective strategy in 10 steps from commercially available starting materials. Binding affinities of 1 at native ionotropic Glu receptors were determined to be in the micromolar range (AMPA, 51 µM; KA, 22 µM; NMDA 6 µM), with the highest affinity for cloned homomeric KA receptor subtypes GluK1,3 (3.0 and 8.1 µM, respectively). Functional characterization of 1 by two electrode voltage clamp (TEVC) electrophysiology at a nondesensitizing mutant of GluK1 showed full competitive antagonistic behavior with a Kb of 11.4 µM.

U2 - 10.1021/cn100093f

DO - 10.1021/cn100093f

M3 - Journal article

VL - 2

SP - 107

EP - 114

JO - A C S Chemical Neuroscience

JF - A C S Chemical Neuroscience

SN - 1948-7193

IS - 2

ER -

ID: 32639600