ArticleACS medicinal chemistry letters2014
Structure-Based Design of Reactive Nucleosides for Site-Specific Modification of the A2A Adenosine Receptor.
Article in ACS medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- A modular click ligand-directed approach to label endogenous dopamine DCommunications chemistry · 2025Article
- Covalent functionalization of G protein-coupled receptors by small molecular probes.RSC chemical biology · 2025Review
- Ligand-Directed Labeling of the Adenosine AJournal of medicinal chemistry · 2024Article
- Article
- Optimization of Peptide Linker-Based Fluorescent Ligands for the Histamine HJournal of medicinal chemistry · 2022Article
- International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update.Pharmacological reviews · 2022Review
- Detection of genome-edited and endogenously expressed G protein-coupled receptors.The FEBS journal · 2021Review
- Design and Characterization of an Intracellular Covalent Ligand for CC Chemokine Receptor 2.Journal of medicinal chemistry · 2021Article
- Molecular probes for the human adenosine receptors.Purinergic signalling · 2021Review
- Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells.Communications biology · 2020Article
- Covalent Inhibition of the Histamine HMolecules (Basel, Switzerland) · 2019Article
- Chemical Probes for the Adenosine Receptors.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Photoaffinity Labeling of the Human AACS medicinal chemistry letters · 2017Article
- A covalent antagonist for the human adenosine APurinergic signalling · 2017Article
- John Daly Lecture: Structure-guided Drug Design for Adenosine and P2Y Receptors.Computational and structural biotechnology journal · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Adenosine receptors (ARs) are members of the G protein-coupled receptor (GPCR) superfamily and have shown much promise as therapeutic targets. We have used an agonist-bound A2AAR X-ray crystallographic structure to design a chemically reactive agonist for site-specific chemical modification of the receptor. To further explore and chemically engineer its binding cavity, a 2-nitrophenyl active ester was attached through an elongated chain at adenine C2 position. This general structure was designed for irreversible transfer of a terminal acyl group to a nucleophilic amino group on the A2AAR. Preincubation with several O-acyl derivatives prevented radioligand binding that was not regenerated upon extensive washing. In silico receptor docking suggested two lysine residues (second extracellular loop) as potential target sites for an O-acetyl derivative (MRS5854, 3a), and site-directed mutagenesis indicated that K153 but not K150 is essential. Similarly, a butyl azide for click reaction was incorporated in the active ester moiety (3b). These promising results indicate a stable, covalent modification of the receptor by several reactive adenosine derivatives, which could be chemical tools for future imaging, structural probing, and drug discovery. Thus, structure-based ligand design has guided the site-specific modification of a GPCR.
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Registered trials
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