Design, synthesis, and biological evaluation of bivalent ligands targeting dopamine D2-like receptors and the μ-opioid receptor
- Author
- Mingcheng Qian, Lakshmi Vasudevan, Jelle Huysentruyt, Martijn Risseeuw (UGent) , Christophe Stove (UGent) , Patrick ML Vanderheyden, Kathleen Van Craenenbroeck (UGent) and Serge Van Calenbergh (UGent)
- Organization
- Abstract
- Currently, there is mounting evidence that intermolecular receptor-receptor interactions may result in altered receptor recognition, pharmacology and signaling. Heterobivalent ligands have been proven useful as molecular probes for confirming and targeting heteromeric receptors. This report describes the design and synthesis of novel heterobivalent ligands for dopamine D-2-like receptors (D-2-likeR) and the -opioid receptor (OR) and their evaluation using ligand binding and functional assays. Interestingly, we identified a potent bivalent ligand that contains a short 18-atom linker and combines good potency with high efficacy both in -arrestin2 recruitment for OR and MAPK-P for D4R. Furthermore, this compound was characterized by a biphasic competition binding curve for the D4R-OR heterodimer, indicative of a bivalent binding mode. As this compound possibly bridges the D4R-OR heterodimer, it could be used as a pharmacological tool to further investigate the interactions of D4R and OR.
- Keywords
- bivalent ligands, dopamine D-2-like receptors, ligand binding, signal transduction, -opioid receptors, RAT STRIATUM, AGONIST, PHARMACOPHORES, ANTAGONIST, EXPRESSION, BINDING, D2, UBIQUITINATION, DIMERIZATION, MODULATION
Downloads
-
(...).pdf
- full text
- |
- UGent only
- |
- |
- 1.47 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8565564
- MLA
- Qian, Mingcheng, et al. “Design, Synthesis, and Biological Evaluation of Bivalent Ligands Targeting Dopamine D2-like Receptors and the μ-Opioid Receptor.” CHEMMEDCHEM, vol. 13, no. 9, 2018, pp. 944–56, doi:10.1002/cmdc.201700787.
- APA
- Qian, M., Vasudevan, L., Huysentruyt, J., Risseeuw, M., Stove, C., Vanderheyden, P. M., … Van Calenbergh, S. (2018). Design, synthesis, and biological evaluation of bivalent ligands targeting dopamine D2-like receptors and the μ-opioid receptor. CHEMMEDCHEM, 13(9), 944–956. https://doi.org/10.1002/cmdc.201700787
- Chicago author-date
- Qian, Mingcheng, Lakshmi Vasudevan, Jelle Huysentruyt, Martijn Risseeuw, Christophe Stove, Patrick ML Vanderheyden, Kathleen Van Craenenbroeck, and Serge Van Calenbergh. 2018. “Design, Synthesis, and Biological Evaluation of Bivalent Ligands Targeting Dopamine D2-like Receptors and the μ-Opioid Receptor.” CHEMMEDCHEM 13 (9): 944–56. https://doi.org/10.1002/cmdc.201700787.
- Chicago author-date (all authors)
- Qian, Mingcheng, Lakshmi Vasudevan, Jelle Huysentruyt, Martijn Risseeuw, Christophe Stove, Patrick ML Vanderheyden, Kathleen Van Craenenbroeck, and Serge Van Calenbergh. 2018. “Design, Synthesis, and Biological Evaluation of Bivalent Ligands Targeting Dopamine D2-like Receptors and the μ-Opioid Receptor.” CHEMMEDCHEM 13 (9): 944–956. doi:10.1002/cmdc.201700787.
- Vancouver
- 1.Qian M, Vasudevan L, Huysentruyt J, Risseeuw M, Stove C, Vanderheyden PM, et al. Design, synthesis, and biological evaluation of bivalent ligands targeting dopamine D2-like receptors and the μ-opioid receptor. CHEMMEDCHEM. 2018;13(9):944–56.
- IEEE
- [1]M. Qian et al., “Design, synthesis, and biological evaluation of bivalent ligands targeting dopamine D2-like receptors and the μ-opioid receptor,” CHEMMEDCHEM, vol. 13, no. 9, pp. 944–956, 2018.
@article{8565564,
abstract = {{Currently, there is mounting evidence that intermolecular receptor-receptor interactions may result in altered receptor recognition, pharmacology and signaling. Heterobivalent ligands have been proven useful as molecular probes for confirming and targeting heteromeric receptors. This report describes the design and synthesis of novel heterobivalent ligands for dopamine D-2-like receptors (D-2-likeR) and the -opioid receptor (OR) and their evaluation using ligand binding and functional assays. Interestingly, we identified a potent bivalent ligand that contains a short 18-atom linker and combines good potency with high efficacy both in -arrestin2 recruitment for OR and MAPK-P for D4R. Furthermore, this compound was characterized by a biphasic competition binding curve for the D4R-OR heterodimer, indicative of a bivalent binding mode. As this compound possibly bridges the D4R-OR heterodimer, it could be used as a pharmacological tool to further investigate the interactions of D4R and OR.}},
author = {{Qian, Mingcheng and Vasudevan, Lakshmi and Huysentruyt, Jelle and Risseeuw, Martijn and Stove, Christophe and Vanderheyden, Patrick ML and Van Craenenbroeck, Kathleen and Van Calenbergh, Serge}},
issn = {{1860-7179}},
journal = {{CHEMMEDCHEM}},
keywords = {{bivalent ligands,dopamine D-2-like receptors,ligand binding,signal transduction,-opioid receptors,RAT STRIATUM,AGONIST,PHARMACOPHORES,ANTAGONIST,EXPRESSION,BINDING,D2,UBIQUITINATION,DIMERIZATION,MODULATION}},
language = {{eng}},
number = {{9}},
pages = {{944--956}},
title = {{Design, synthesis, and biological evaluation of bivalent ligands targeting dopamine D2-like receptors and the μ-opioid receptor}},
url = {{http://doi.org/10.1002/cmdc.201700787}},
volume = {{13}},
year = {{2018}},
}
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: