ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Figure 1Loading Img
RETURN TO ISSUEPREVResearch ArticleNEXT

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

  • Christian B. M. Poulie*
    Christian B. M. Poulie
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
    *Email: [email protected]
  • Younes Larsen
    Younes Larsen
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
  • Cindie Leteneur
    Cindie Leteneur
    Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, Université de Bordeaux, CNRS, F-33000 Bordeaux, France
  • Gaël Barthet
    Gaël Barthet
    Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, Université de Bordeaux, CNRS, F-33000 Bordeaux, France
  • Walden E. Bjørn-Yoshimoto
    Walden E. Bjørn-Yoshimoto
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
  • Fanny Malhaire
    Fanny Malhaire
    IGF, INSERM, Université de Montpellier, CNRS, F-34094 Montpellier, France
  • Birgitte Nielsen
    Birgitte Nielsen
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
  • Jean-Phillippe Pin
    Jean-Phillippe Pin
    IGF, INSERM, Université de Montpellier, CNRS, F-34094 Montpellier, France
  • Christophe Mulle
    Christophe Mulle
    Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, Université de Bordeaux, CNRS, F-33000 Bordeaux, France
  • Darryl S. Pickering
    Darryl S. Pickering
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
  • , and 
  • Lennart Bunch*
    Lennart Bunch
    Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
    *Email: [email protected]
Cite this: ACS Chem. Neurosci. 2022, 13, 10, 1580–1587
Publication Date (Web):April 27, 2022
https://doi.org/10.1021/acschemneuro.2c00162
Copyright © 2022 American Chemical Society

    Article Views

    561

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options

    Abstract

    Abstract Image

    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.

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. You can change your affiliated institution below.

    Cited By

    This article is cited by 2 publications.

    1. Paulina Chałupnik, Ewa Szymańska. Kainate Receptor Antagonists: Recent Advances and Therapeutic Perspective. International Journal of Molecular Sciences 2023, 24 (3) , 1908. https://doi.org/10.3390/ijms24031908
    2. Paulina Chałupnik, Alina Vialko, Darryl S. Pickering, Markus Hinkkanen, Stephanie Donbosco, Thor C. Møller, Anders A. Jensen, Birgitte Nielsen, Yasmin Bay, Anders S. Kristensen, Tommy N. Johansen, Kamil Łątka, Marek Bajda, Ewa Szymańska. Discovery of the First Highly Selective Antagonist of the GluK3 Kainate Receptor Subtype. International Journal of Molecular Sciences 2022, 23 (15) , 8797. https://doi.org/10.3390/ijms23158797

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect