Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands. / Szymańska, Ewa; Chałupnik, Paulina; Johansen, Tommy Nørskov; Nielsen, Birgitte; Cuñado Moral, Ana Maria; Pickering, Darryl S; Kieć-Kononowicz, Katarzyna.

In: Chemical Biology & Drug Design, Vol. 90, 01.12.2017, p. 1271-1281.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Szymańska, E, Chałupnik, P, Johansen, TN, Nielsen, B, Cuñado Moral, AM, Pickering, DS & Kieć-Kononowicz, K 2017, 'Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands', Chemical Biology & Drug Design, vol. 90, pp. 1271-1281. https://doi.org/10.1111/cbdd.13048

APA

Szymańska, E., Chałupnik, P., Johansen, T. N., Nielsen, B., Cuñado Moral, A. M., Pickering, D. S., & Kieć-Kononowicz, K. (2017). Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands. Chemical Biology & Drug Design, 90, 1271-1281. https://doi.org/10.1111/cbdd.13048

Vancouver

Szymańska E, Chałupnik P, Johansen TN, Nielsen B, Cuñado Moral AM, Pickering DS et al. Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands. Chemical Biology & Drug Design. 2017 Dec 1;90:1271-1281. https://doi.org/10.1111/cbdd.13048

Author

Szymańska, Ewa ; Chałupnik, Paulina ; Johansen, Tommy Nørskov ; Nielsen, Birgitte ; Cuñado Moral, Ana Maria ; Pickering, Darryl S ; Kieć-Kononowicz, Katarzyna. / Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands. In: Chemical Biology & Drug Design. 2017 ; Vol. 90. pp. 1271-1281.

Bibtex

@article{b2b0d277d4be402bab5cba504beedad0,
title = "Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands",
abstract = "A series of racemic unnatural amino acids was rationally designed on the basis of recently published X-ray structures of the GluA2 LBD with bound phenylalanine-based antagonists. Twelve new diaryl- or aryl/heteroaryl-substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3'-hydroxy-5-(1H-pyrazol-4-yl)-[1,1'-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4.6 µM for native AMPA receptors and almost 5-fold lower affinity for kainic acid receptors. Furthermore, 7e was evaluated at recombinant homomeric rat GluA2 and GluA3 receptors. Recently reported X-ray structures 5CBR and 5CBS, representing two distinct antagonist binding modes, were used as templates for molecular docking of the synthesized series. Binding data supported with molecular modeling confirmed that aryl/heteroaryl-substituted phenylalanine analogues effectively bind to AMPA receptors with low micromolar affinity and high selectivity over native NMDA and kainate receptors. These properties make 7e a promising lead for the further development of new AMPA receptor ligands.",
author = "Ewa Szymańska and Paulina Chałupnik and Johansen, {Tommy N{\o}rskov} and Birgitte Nielsen and {Cu{\~n}ado Moral}, {Ana Maria} and Pickering, {Darryl S} and Katarzyna Kieć-Kononowicz",
year = "2017",
month = "12",
day = "1",
doi = "10.1111/cbdd.13048",
language = "English",
volume = "90",
pages = "1271--1281",
journal = "Chemical Biology and Drug Design (Print)",
issn = "1747-0277",
publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands

AU - Szymańska, Ewa

AU - Chałupnik, Paulina

AU - Johansen, Tommy Nørskov

AU - Nielsen, Birgitte

AU - Cuñado Moral, Ana Maria

AU - Pickering, Darryl S

AU - Kieć-Kononowicz, Katarzyna

PY - 2017/12/1

Y1 - 2017/12/1

N2 - A series of racemic unnatural amino acids was rationally designed on the basis of recently published X-ray structures of the GluA2 LBD with bound phenylalanine-based antagonists. Twelve new diaryl- or aryl/heteroaryl-substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3'-hydroxy-5-(1H-pyrazol-4-yl)-[1,1'-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4.6 µM for native AMPA receptors and almost 5-fold lower affinity for kainic acid receptors. Furthermore, 7e was evaluated at recombinant homomeric rat GluA2 and GluA3 receptors. Recently reported X-ray structures 5CBR and 5CBS, representing two distinct antagonist binding modes, were used as templates for molecular docking of the synthesized series. Binding data supported with molecular modeling confirmed that aryl/heteroaryl-substituted phenylalanine analogues effectively bind to AMPA receptors with low micromolar affinity and high selectivity over native NMDA and kainate receptors. These properties make 7e a promising lead for the further development of new AMPA receptor ligands.

AB - A series of racemic unnatural amino acids was rationally designed on the basis of recently published X-ray structures of the GluA2 LBD with bound phenylalanine-based antagonists. Twelve new diaryl- or aryl/heteroaryl-substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3'-hydroxy-5-(1H-pyrazol-4-yl)-[1,1'-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4.6 µM for native AMPA receptors and almost 5-fold lower affinity for kainic acid receptors. Furthermore, 7e was evaluated at recombinant homomeric rat GluA2 and GluA3 receptors. Recently reported X-ray structures 5CBR and 5CBS, representing two distinct antagonist binding modes, were used as templates for molecular docking of the synthesized series. Binding data supported with molecular modeling confirmed that aryl/heteroaryl-substituted phenylalanine analogues effectively bind to AMPA receptors with low micromolar affinity and high selectivity over native NMDA and kainate receptors. These properties make 7e a promising lead for the further development of new AMPA receptor ligands.

U2 - 10.1111/cbdd.13048

DO - 10.1111/cbdd.13048

M3 - Journal article

VL - 90

SP - 1271

EP - 1281

JO - Chemical Biology and Drug Design (Print)

JF - Chemical Biology and Drug Design (Print)

SN - 1747-0277

ER -

ID: 170429543