Discovery of a true bivalent dopamine D2 receptor agonist
- Author
- Mingcheng Qian, Adrián Ricarte, Elise Wouters, James A.R. Dalton, Martijn Risseeuw (UGent) , Jesús Giraldo and Serge Van Calenbergh (UGent)
- Organization
- Abstract
- Employing two different alkyne-modified dopamine agonists to construct bivalent compounds via click chemistry resulted in the identification of a bivalent ligand (11c) for dopamine D-2 receptor homodimer, which, compared to its parent monomeric alkyne, showed a 16-fold higher binding affinity for the dopamine D-2 receptor and a 5-fold higher potency in a cAMP assay in HEK 293T cells stably expressing D2R. Molecular modeling revealed that 11c can indeed bridge the orthosteric binding sites of a D2R homodimer in a relaxed conformation via the TM5-TM6 interface and allows to largely rationalize the results of the receptor assays. (C) 2020 Elsevier Masson SAS. All rights reserved.
- Keywords
- Organic Chemistry, Pharmacology, Drug Discovery, General Medicine, Bivalent ligands, D2R homodimer, Binding affinity, cAMP, Molecular modeling
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8713721
- MLA
- Qian, Mingcheng, et al. “Discovery of a True Bivalent Dopamine D2 Receptor Agonist.” EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 212, 2021, doi:10.1016/j.ejmech.2020.113151.
- APA
- Qian, M., Ricarte, A., Wouters, E., Dalton, J. A. R., Risseeuw, M., Giraldo, J., & Van Calenbergh, S. (2021). Discovery of a true bivalent dopamine D2 receptor agonist. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 212. https://doi.org/10.1016/j.ejmech.2020.113151
- Chicago author-date
- Qian, Mingcheng, Adrián Ricarte, Elise Wouters, James A.R. Dalton, Martijn Risseeuw, Jesús Giraldo, and Serge Van Calenbergh. 2021. “Discovery of a True Bivalent Dopamine D2 Receptor Agonist.” EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 212. https://doi.org/10.1016/j.ejmech.2020.113151.
- Chicago author-date (all authors)
- Qian, Mingcheng, Adrián Ricarte, Elise Wouters, James A.R. Dalton, Martijn Risseeuw, Jesús Giraldo, and Serge Van Calenbergh. 2021. “Discovery of a True Bivalent Dopamine D2 Receptor Agonist.” EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 212. doi:10.1016/j.ejmech.2020.113151.
- Vancouver
- 1.Qian M, Ricarte A, Wouters E, Dalton JAR, Risseeuw M, Giraldo J, et al. Discovery of a true bivalent dopamine D2 receptor agonist. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. 2021;212.
- IEEE
- [1]M. Qian et al., “Discovery of a true bivalent dopamine D2 receptor agonist,” EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 212, 2021.
@article{8713721,
abstract = {{Employing two different alkyne-modified dopamine agonists to construct bivalent compounds via click chemistry resulted in the identification of a bivalent ligand (11c) for dopamine D-2 receptor homodimer, which, compared to its parent monomeric alkyne, showed a 16-fold higher binding affinity for the dopamine D-2 receptor and a 5-fold higher potency in a cAMP assay in HEK 293T cells stably expressing D2R. Molecular modeling revealed that 11c can indeed bridge the orthosteric binding sites of a D2R homodimer in a relaxed conformation via the TM5-TM6 interface and allows to largely rationalize the results of the receptor assays. (C) 2020 Elsevier Masson SAS. All rights reserved.}},
articleno = {{113151}},
author = {{Qian, Mingcheng and Ricarte, Adrián and Wouters, Elise and Dalton, James A.R. and Risseeuw, Martijn and Giraldo, Jesús and Van Calenbergh, Serge}},
issn = {{0223-5234}},
journal = {{EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY}},
keywords = {{Organic Chemistry,Pharmacology,Drug Discovery,General Medicine,Bivalent ligands,D2R homodimer,Binding affinity,cAMP,Molecular modeling}},
language = {{eng}},
pages = {{11}},
title = {{Discovery of a true bivalent dopamine D2 receptor agonist}},
url = {{http://doi.org/10.1016/j.ejmech.2020.113151}},
volume = {{212}},
year = {{2021}},
}
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