A Diversity Oriented Synthesis Approach to New 2,3-trans-Substituted l-Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors

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

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A Diversity Oriented Synthesis Approach to New 2,3-trans-Substituted l-Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors. / Kayser, Silke; Temperini, Piero; Poulie, Christian B M; Staudt, Markus; Nielsen, Birgitte; Pickering, Darryl S; Bunch, Lennart.

In: ACS Chemical Neuroscience, Vol. 11, 04.03.2020, p. 702-714.

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

Harvard

Kayser, S, Temperini, P, Poulie, CBM, Staudt, M, Nielsen, B, Pickering, DS & Bunch, L 2020, 'A Diversity Oriented Synthesis Approach to New 2,3-trans-Substituted l-Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors', ACS Chemical Neuroscience, vol. 11, pp. 702-714. https://doi.org/10.1021/acschemneuro.0c00005

APA

Kayser, S., Temperini, P., Poulie, C. B. M., Staudt, M., Nielsen, B., Pickering, D. S., & Bunch, L. (2020). A Diversity Oriented Synthesis Approach to New 2,3-trans-Substituted l-Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors. ACS Chemical Neuroscience, 11, 702-714. https://doi.org/10.1021/acschemneuro.0c00005

Vancouver

Kayser S, Temperini P, Poulie CBM, Staudt M, Nielsen B, Pickering DS et al. A Diversity Oriented Synthesis Approach to New 2,3-trans-Substituted l-Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors. ACS Chemical Neuroscience. 2020 Mar 4;11:702-714. https://doi.org/10.1021/acschemneuro.0c00005

Author

Kayser, Silke ; Temperini, Piero ; Poulie, Christian B M ; Staudt, Markus ; Nielsen, Birgitte ; Pickering, Darryl S ; Bunch, Lennart. / A Diversity Oriented Synthesis Approach to New 2,3-trans-Substituted l-Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors. In: ACS Chemical Neuroscience. 2020 ; Vol. 11. pp. 702-714.

Bibtex

@article{4788a81430bc450aa874e44b06a8c973,
title = "A Diversity Oriented Synthesis Approach to New 2,3-trans-Substituted l-Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors",
abstract = "Discovery of chemical tools for the ionotropic glutamate receptors continues to be a challenging task. Herein we report a diversity-oriented approach to new 2,3-trans-l-proline analogs whereby we study how the spatial orientation of the distal carboxylate group influences the binding affinity and receptor class and subtype selectivity. In total, 10 new analogs were synthesized and 14 stereoisomers characterized in binding assays at native rat ionotropic glutamate receptors, and at cloned human homomeric kainic acid (KA) receptor subtypes GluK1-3. The study identified isoxazole analogs 3d,e, which displayed selectivity in binding at native N-methyl-d-aspartate (NMDA) receptors over native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and KA receptors, in the high nanomolar to low micromolar range. Furthermore, analogs 3i-A/B showed a preference in binding affinity for GluK3 over GluK1,2. Finally, analog 3j displayed high nanomolar affinity for native NMDA receptors as well as for homomeric GluK3 receptors.",
author = "Silke Kayser and Piero Temperini and Poulie, {Christian B M} and Markus Staudt and Birgitte Nielsen and Pickering, {Darryl S} and Lennart Bunch",
year = "2020",
month = mar,
day = "4",
doi = "10.1021/acschemneuro.0c00005",
language = "English",
volume = "11",
pages = "702--714",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - A Diversity Oriented Synthesis Approach to New 2,3-trans-Substituted l-Proline Analogs as Potential Ligands for the Ionotropic Glutamate Receptors

AU - Kayser, Silke

AU - Temperini, Piero

AU - Poulie, Christian B M

AU - Staudt, Markus

AU - Nielsen, Birgitte

AU - Pickering, Darryl S

AU - Bunch, Lennart

PY - 2020/3/4

Y1 - 2020/3/4

N2 - Discovery of chemical tools for the ionotropic glutamate receptors continues to be a challenging task. Herein we report a diversity-oriented approach to new 2,3-trans-l-proline analogs whereby we study how the spatial orientation of the distal carboxylate group influences the binding affinity and receptor class and subtype selectivity. In total, 10 new analogs were synthesized and 14 stereoisomers characterized in binding assays at native rat ionotropic glutamate receptors, and at cloned human homomeric kainic acid (KA) receptor subtypes GluK1-3. The study identified isoxazole analogs 3d,e, which displayed selectivity in binding at native N-methyl-d-aspartate (NMDA) receptors over native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and KA receptors, in the high nanomolar to low micromolar range. Furthermore, analogs 3i-A/B showed a preference in binding affinity for GluK3 over GluK1,2. Finally, analog 3j displayed high nanomolar affinity for native NMDA receptors as well as for homomeric GluK3 receptors.

AB - Discovery of chemical tools for the ionotropic glutamate receptors continues to be a challenging task. Herein we report a diversity-oriented approach to new 2,3-trans-l-proline analogs whereby we study how the spatial orientation of the distal carboxylate group influences the binding affinity and receptor class and subtype selectivity. In total, 10 new analogs were synthesized and 14 stereoisomers characterized in binding assays at native rat ionotropic glutamate receptors, and at cloned human homomeric kainic acid (KA) receptor subtypes GluK1-3. The study identified isoxazole analogs 3d,e, which displayed selectivity in binding at native N-methyl-d-aspartate (NMDA) receptors over native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and KA receptors, in the high nanomolar to low micromolar range. Furthermore, analogs 3i-A/B showed a preference in binding affinity for GluK3 over GluK1,2. Finally, analog 3j displayed high nanomolar affinity for native NMDA receptors as well as for homomeric GluK3 receptors.

U2 - 10.1021/acschemneuro.0c00005

DO - 10.1021/acschemneuro.0c00005

M3 - Journal article

C2 - 32069018

VL - 11

SP - 702

EP - 714

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

ER -

ID: 237104712