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Discovery of a true bivalent dopamine D2 receptor agonist

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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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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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