Stereoselective synthesis of novel 2′-(S)-CCG-IV analogues as potent NMDA receptor agonists

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

Standard

Stereoselective synthesis of novel 2′-(S)-CCG-IV analogues as potent NMDA receptor agonists. / Maolanon, Alex; Papangelis, Athanasios; Kawiecki, David; Mou, Tung Chung; Syrenne, Jed T.; Yi, Feng; Hansen, Kasper B.; Clausen, Rasmus P.

In: European Journal of Medicinal Chemistry, Vol. 212, 113099, 2021.

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

Harvard

Maolanon, A, Papangelis, A, Kawiecki, D, Mou, TC, Syrenne, JT, Yi, F, Hansen, KB & Clausen, RP 2021, 'Stereoselective synthesis of novel 2′-(S)-CCG-IV analogues as potent NMDA receptor agonists', European Journal of Medicinal Chemistry, vol. 212, 113099. https://doi.org/10.1016/j.ejmech.2020.113099

APA

Maolanon, A., Papangelis, A., Kawiecki, D., Mou, T. C., Syrenne, J. T., Yi, F., Hansen, K. B., & Clausen, R. P. (2021). Stereoselective synthesis of novel 2′-(S)-CCG-IV analogues as potent NMDA receptor agonists. European Journal of Medicinal Chemistry, 212, [113099]. https://doi.org/10.1016/j.ejmech.2020.113099

Vancouver

Maolanon A, Papangelis A, Kawiecki D, Mou TC, Syrenne JT, Yi F et al. Stereoselective synthesis of novel 2′-(S)-CCG-IV analogues as potent NMDA receptor agonists. European Journal of Medicinal Chemistry. 2021;212. 113099. https://doi.org/10.1016/j.ejmech.2020.113099

Author

Maolanon, Alex ; Papangelis, Athanasios ; Kawiecki, David ; Mou, Tung Chung ; Syrenne, Jed T. ; Yi, Feng ; Hansen, Kasper B. ; Clausen, Rasmus P. / Stereoselective synthesis of novel 2′-(S)-CCG-IV analogues as potent NMDA receptor agonists. In: European Journal of Medicinal Chemistry. 2021 ; Vol. 212.

Bibtex

@article{6a032034867745d6a5bdd570da0063c2,
title = "Stereoselective synthesis of novel 2′-(S)-CCG-IV analogues as potent NMDA receptor agonists",
abstract = "We developed a versatile stereoselective route for the synthesis of new 2′-(S)-CCG-IV analogues. The route allows for late stage diversification and thereby provides access to a great variety of conformationally restricted cyclopropyl glutamate analogues. A selection of the 2′-(S)-CCG-IV analogues were evaluated using two-electrode voltage-clamp electrophysiology at recombinant GluN1/GluN2A-D receptors, demonstrating that agonists can be developed with GluN2 subunit-dependent potency and agonist efficacy. We also describe a crystal structure of the GluN2A agonist binding domain in complex with 2′-butyl-(S)-CCG-IV that determines the position of 2′-substituents in (S)-CCG-IV agonists in the glutamate binding site and provides further insight to the structural determinants of their agonist efficacy. The stereoselective synthesis described here enables versatile and straight-forward modifications to diverse analogues of interest for the development of potent subtype-specific NMDA receptor agonists and other applications.",
keywords = "(carboxycyclopropyl)glycine, NMDA, Synthesis, X-ray crystallography",
author = "Alex Maolanon and Athanasios Papangelis and David Kawiecki and Mou, {Tung Chung} and Syrenne, {Jed T.} and Feng Yi and Hansen, {Kasper B.} and Clausen, {Rasmus P.}",
year = "2021",
doi = "10.1016/j.ejmech.2020.113099",
language = "English",
volume = "212",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson",

}

RIS

TY - JOUR

T1 - Stereoselective synthesis of novel 2′-(S)-CCG-IV analogues as potent NMDA receptor agonists

AU - Maolanon, Alex

AU - Papangelis, Athanasios

AU - Kawiecki, David

AU - Mou, Tung Chung

AU - Syrenne, Jed T.

AU - Yi, Feng

AU - Hansen, Kasper B.

AU - Clausen, Rasmus P.

PY - 2021

Y1 - 2021

N2 - We developed a versatile stereoselective route for the synthesis of new 2′-(S)-CCG-IV analogues. The route allows for late stage diversification and thereby provides access to a great variety of conformationally restricted cyclopropyl glutamate analogues. A selection of the 2′-(S)-CCG-IV analogues were evaluated using two-electrode voltage-clamp electrophysiology at recombinant GluN1/GluN2A-D receptors, demonstrating that agonists can be developed with GluN2 subunit-dependent potency and agonist efficacy. We also describe a crystal structure of the GluN2A agonist binding domain in complex with 2′-butyl-(S)-CCG-IV that determines the position of 2′-substituents in (S)-CCG-IV agonists in the glutamate binding site and provides further insight to the structural determinants of their agonist efficacy. The stereoselective synthesis described here enables versatile and straight-forward modifications to diverse analogues of interest for the development of potent subtype-specific NMDA receptor agonists and other applications.

AB - We developed a versatile stereoselective route for the synthesis of new 2′-(S)-CCG-IV analogues. The route allows for late stage diversification and thereby provides access to a great variety of conformationally restricted cyclopropyl glutamate analogues. A selection of the 2′-(S)-CCG-IV analogues were evaluated using two-electrode voltage-clamp electrophysiology at recombinant GluN1/GluN2A-D receptors, demonstrating that agonists can be developed with GluN2 subunit-dependent potency and agonist efficacy. We also describe a crystal structure of the GluN2A agonist binding domain in complex with 2′-butyl-(S)-CCG-IV that determines the position of 2′-substituents in (S)-CCG-IV agonists in the glutamate binding site and provides further insight to the structural determinants of their agonist efficacy. The stereoselective synthesis described here enables versatile and straight-forward modifications to diverse analogues of interest for the development of potent subtype-specific NMDA receptor agonists and other applications.

KW - (carboxycyclopropyl)glycine

KW - NMDA

KW - Synthesis

KW - X-ray crystallography

U2 - 10.1016/j.ejmech.2020.113099

DO - 10.1016/j.ejmech.2020.113099

M3 - Journal article

C2 - 33383257

AN - SCOPUS:85098177490

VL - 212

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

M1 - 113099

ER -

ID: 256508902