ArticleActa pharmacologica Sinica2013
Design, synthesis and biological evaluation of bivalent ligands against A(1)-D(1) receptor heteromers.
Article in Acta pharmacologica Sinica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Adenosine in the Brain: Recent Progress on Detection, Function, and Translation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Hibifolin, a Natural Sortase A Inhibitor, Attenuates the Pathogenicity of Staphylococcus aureus and Enhances the Antibacterial Activity of Cefotaxime.Microbiology spectrum · 2022Article
- 2016 Philip S. Portoghese Medicinal Chemistry Lectureship: Designing Bivalent or Bitopic Molecules for G-Protein Coupled Receptors. The Whole Is Greater Than the Sum of Its Parts.Journal of medicinal chemistry · 2020Article
- Adenosine AMolecular neurobiology · 2019Article
- Functional Cross-Talk between Adenosine and Metabotropic Glutamate Receptors.Current neuropharmacology · 2019Review
- New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism.British journal of pharmacology · 2018Review
- Receptor-Receptor Interactions of G Protein-Coupled Receptors in the Carotid Body: A Working Hypothesis.Frontiers in physiology · 2018Article
- Neurochemical evidence supporting dopamine D1-D2 receptor heteromers in the striatum of the long-tailed macaque: changes following dopaminergic manipulation.Brain structure & function · 2017Article
- Developmental origins of brain disorders: roles for dopamine.Frontiers in cellular neuroscience · 2013Review
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Authors and funding
9 authors.
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Abstract
aimTo design and synthesize bivalent ligands for adenosine A1-dopamine D1 receptor heteromers (A1-D1R), and evaluate their pharmacological activities.
methodsBivalent ligands and their corresponding A1R monovalent ligands were designed and synthesized. The affinities of the bivalent ligands for A1R and D1R in rat brain membrane preparation were examined using radiolabeled binding assays. To demonstrate the formation of A1-D1R, fluorescence resonance energy transfer (FRET) was conducted in HEK293 cells transfected with D1-CFP and A1-YFP. Molecular modeling was used to analyze the possible mode of protein-protein and protein-ligand interactions.
resultsTwo bivalent ligands for A1R and D1R (20a, 20b), as well as the corresponding A1R monovalent ligands (21a, 21b) were synthesized. In radiolabeled binding assays, the bivalent ligands showed affinities for A1R 10-100 times higher than those of the corresponding monovalent ligands. In FRET experiments, the bivalent ligands significantly increased the heterodimerization of A1R and D1R compared with the corresponding monovalent ligands. A heterodimer model with the interface of helixes 3, 4, 5 of A1R and helixes 1, 6, 7 from D1R was established with molecular modeling. The distance between the two ligand binding sites in the heterodimer model was approximately 48.4 Å, which was shorter than the length of the bivalent ligands.
conclusionThis study demonstrates the existence of A1-D1R in situ and a simultaneous interaction of bivalent ligands with both the receptors.
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