(S)-2-Mercaptohistidine: A First Selective Orthosteric GluK3 Antagonist

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

Standard

(S)-2-Mercaptohistidine : A First Selective Orthosteric GluK3 Antagonist. / Poulie, Christian B.M.; Larsen, Younes; Leteneur, Cindie; Barthet, Gael; Bjorn-Yoshimoto, Walden E.; Malhaire, Fanny; Nielsen, Birgitte; Pin, Jean Phillippe; Mulle, Christophe; Pickering, Darryl S.; Bunch, Lennart.

In: ACS Chemical Neuroscience, Vol. 13, No. 10, 2022, p. 1580–1587.

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

Harvard

Poulie, CBM, Larsen, Y, Leteneur, C, Barthet, G, Bjorn-Yoshimoto, WE, Malhaire, F, Nielsen, B, Pin, JP, Mulle, C, Pickering, DS & Bunch, L 2022, '(S)-2-Mercaptohistidine: A First Selective Orthosteric GluK3 Antagonist', ACS Chemical Neuroscience, vol. 13, no. 10, pp. 1580–1587. https://doi.org/10.1021/acschemneuro.2c00162

APA

Poulie, C. B. M., Larsen, Y., Leteneur, C., Barthet, G., Bjorn-Yoshimoto, W. E., Malhaire, F., Nielsen, B., Pin, J. P., Mulle, C., Pickering, D. S., & Bunch, L. (2022). (S)-2-Mercaptohistidine: A First Selective Orthosteric GluK3 Antagonist. ACS Chemical Neuroscience, 13(10), 1580–1587. https://doi.org/10.1021/acschemneuro.2c00162

Vancouver

Poulie CBM, Larsen Y, Leteneur C, Barthet G, Bjorn-Yoshimoto WE, Malhaire F et al. (S)-2-Mercaptohistidine: A First Selective Orthosteric GluK3 Antagonist. ACS Chemical Neuroscience. 2022;13(10):1580–1587. https://doi.org/10.1021/acschemneuro.2c00162

Author

Poulie, Christian B.M. ; Larsen, Younes ; Leteneur, Cindie ; Barthet, Gael ; Bjorn-Yoshimoto, Walden E. ; Malhaire, Fanny ; Nielsen, Birgitte ; Pin, Jean Phillippe ; Mulle, Christophe ; Pickering, Darryl S. ; Bunch, Lennart. / (S)-2-Mercaptohistidine : A First Selective Orthosteric GluK3 Antagonist. In: ACS Chemical Neuroscience. 2022 ; Vol. 13, No. 10. pp. 1580–1587.

Bibtex

@article{e1dd1200b9ee4939bce4d0c91130160f,
title = "(S)-2-Mercaptohistidine: A First Selective Orthosteric GluK3 Antagonist",
abstract = "The development of tool compounds for the ionotropic glutamate receptors (iGluRs) remains an important research objective, as these are essential for the study and understanding of the roles of these receptors in health and disease. Herein, we report on the pharmacological characterization of (S)-2-hydroxyhistidine (2a) and (S)-2-mercaptohistidine (2b) as mediators of glutamatergic neurotransmission. While 2a displayed negligible binding affinity or activity at all glutamate receptors and transporters investigated, 2b displayed selectivity for homomeric GluK3 with binding affinities in the low micromolar range (Ki = 6.42 ± 0.74 μM). The iGluR subtype selectivity ratio for 2b was calculated at 30-fold for GluK1/GluK3, GluA3/GluK3, and GluA4/GluK3 and >100-fold for GluK2/GluK3, GluA1/GluK3, and GluA2/GluK3. Unexpectedly, functional characterization of 2b revealed that the compound is an antagonist (Kb = 7.6 μM) at homomeric GluK3 receptors while exhibiting only weak agonist activity at GluA2 (EC50 = 3.25 ± 0.55 mM). The functional properties of 2b were explored further in electrophysiological recordings of mouse hippocampal neurons. ",
keywords = "amino acid, CNS, GluK3, glutamate receptors, kainate",
author = "Poulie, {Christian B.M.} and Younes Larsen and Cindie Leteneur and Gael Barthet and Bjorn-Yoshimoto, {Walden E.} and Fanny Malhaire and Birgitte Nielsen and Pin, {Jean Phillippe} and Christophe Mulle and Pickering, {Darryl S.} and Lennart Bunch",
note = "Funding Information: The authors thank the University of Copenhagen for the financial support. Anders A. Jensen is acknowledged for the use of the EAAT1–3-HEK293 cells. J.-P.P. acknowledges the Arp{\`e}ge platform of the Institut de G{\'e}nomique Fonctionnelle for providing facilities and technical support and PerkinElmer Cisbio for providing reagents. J.-P.P. was supported by the CNRS, INSERM and the Fondation Recherche M{\'e}dicale (FRM) (Equipe DEQ20170336747). ",
year = "2022",
doi = "10.1021/acschemneuro.2c00162",
language = "English",
volume = "13",
pages = "1580–1587",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - (S)-2-Mercaptohistidine

T2 - A First Selective Orthosteric GluK3 Antagonist

AU - Poulie, Christian B.M.

AU - Larsen, Younes

AU - Leteneur, Cindie

AU - Barthet, Gael

AU - Bjorn-Yoshimoto, Walden E.

AU - Malhaire, Fanny

AU - Nielsen, Birgitte

AU - Pin, Jean Phillippe

AU - Mulle, Christophe

AU - Pickering, Darryl S.

AU - Bunch, Lennart

N1 - Funding Information: The authors thank the University of Copenhagen for the financial support. Anders A. Jensen is acknowledged for the use of the EAAT1–3-HEK293 cells. J.-P.P. acknowledges the Arpège platform of the Institut de Génomique Fonctionnelle for providing facilities and technical support and PerkinElmer Cisbio for providing reagents. J.-P.P. was supported by the CNRS, INSERM and the Fondation Recherche Médicale (FRM) (Equipe DEQ20170336747).

PY - 2022

Y1 - 2022

N2 - The development of tool compounds for the ionotropic glutamate receptors (iGluRs) remains an important research objective, as these are essential for the study and understanding of the roles of these receptors in health and disease. Herein, we report on the pharmacological characterization of (S)-2-hydroxyhistidine (2a) and (S)-2-mercaptohistidine (2b) as mediators of glutamatergic neurotransmission. While 2a displayed negligible binding affinity or activity at all glutamate receptors and transporters investigated, 2b displayed selectivity for homomeric GluK3 with binding affinities in the low micromolar range (Ki = 6.42 ± 0.74 μM). The iGluR subtype selectivity ratio for 2b was calculated at 30-fold for GluK1/GluK3, GluA3/GluK3, and GluA4/GluK3 and >100-fold for GluK2/GluK3, GluA1/GluK3, and GluA2/GluK3. Unexpectedly, functional characterization of 2b revealed that the compound is an antagonist (Kb = 7.6 μM) at homomeric GluK3 receptors while exhibiting only weak agonist activity at GluA2 (EC50 = 3.25 ± 0.55 mM). The functional properties of 2b were explored further in electrophysiological recordings of mouse hippocampal neurons.

AB - The development of tool compounds for the ionotropic glutamate receptors (iGluRs) remains an important research objective, as these are essential for the study and understanding of the roles of these receptors in health and disease. Herein, we report on the pharmacological characterization of (S)-2-hydroxyhistidine (2a) and (S)-2-mercaptohistidine (2b) as mediators of glutamatergic neurotransmission. While 2a displayed negligible binding affinity or activity at all glutamate receptors and transporters investigated, 2b displayed selectivity for homomeric GluK3 with binding affinities in the low micromolar range (Ki = 6.42 ± 0.74 μM). The iGluR subtype selectivity ratio for 2b was calculated at 30-fold for GluK1/GluK3, GluA3/GluK3, and GluA4/GluK3 and >100-fold for GluK2/GluK3, GluA1/GluK3, and GluA2/GluK3. Unexpectedly, functional characterization of 2b revealed that the compound is an antagonist (Kb = 7.6 μM) at homomeric GluK3 receptors while exhibiting only weak agonist activity at GluA2 (EC50 = 3.25 ± 0.55 mM). The functional properties of 2b were explored further in electrophysiological recordings of mouse hippocampal neurons.

KW - amino acid

KW - CNS

KW - GluK3

KW - glutamate receptors

KW - kainate

U2 - 10.1021/acschemneuro.2c00162

DO - 10.1021/acschemneuro.2c00162

M3 - Journal article

C2 - 35475632

AN - SCOPUS:85129315586

VL - 13

SP - 1580

EP - 1587

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 10

ER -

ID: 308038402