ArticleProceedings of the National Academy of Sciences of the United States of America2014
Covalent agonists for studying G protein-coupled receptor activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 98 citations in OpenAlex.
- Atomic, structural and molecular insights into GPCR ligand binding and signalling.Nature reviews. Molecular cell biology · 2026Review
- A Minimalist Model for Navigating Conformational Landscape Uncovers the Activation Mechanism of βACS physical chemistry Au · 2026Article
- Structural Mechanism of an Efficacy Photoswitch Targeting the βAngewandte Chemie (International ed. in English) · 2026Article
- Synthesis and Characterization of Photoswitchable Covalent Ligands for the βAngewandte Chemie (International ed. in English) · 2025Article
- G Protein-Coupled Receptor-Ligand Pose and Functional Class Prediction.International journal of molecular sciences · 2024Article
- Technologies for Direct Detection of Covalent Protein-Drug Adducts.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Homology Modeling of the G Protein-Coupled Receptors.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Photochromic Fentanyl Derivatives for Controlled μ-Opioid Receptor Activation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Photoswitchable Serotonins for Optical Control of the 5-HTAngewandte Chemie (International ed. in English) · 2022Article
- New Chemical Biology Tools for the Histamine Receptor Family.Current topics in behavioral neurosciences · 2022Article
- Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- Universal Properties and Specificities of the βInternational journal of molecular sciences · 2021Article
- 2D SIFt: a matrix of ligand-receptor interactions.Journal of cheminformatics · 2021Article
- Ligands of Adrenergic Receptors: A Structural Point of View.Biomolecules · 2021Review
- Dynamical Correlations Reveal Allosteric Sites in G Protein-Coupled Receptors.International journal of molecular sciences · 2020Article
- Modulation of Amyloidogenic Protein Self-Assembly Using Tethered Small Molecules.Journal of the American Chemical Society · 2020Article
- Covalent allosteric modulation: An emerging strategy for GPCRs drug discovery.European journal of medicinal chemistry · 2020Review
- Synthesis, Radiosynthesis and Biological Evaluation of Buprenorphine-Derived Phenylazocarboxamides as Novel μ-Opioid Receptor Ligands.ChemMedChem · 2020Article
- G Protein-Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action.Pharmacological reviews · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Structural studies on G protein-coupled receptors (GPCRs) provide important insights into the architecture and function of these important drug targets. However, the crystallization of GPCRs in active states is particularly challenging, requiring the formation of stable and conformationally homogeneous ligand-receptor complexes. Native hormones, neurotransmitters, and synthetic agonists that bind with low affinity are ineffective at stabilizing an active state for crystallogenesis. To promote structural studies on the pharmacologically highly relevant class of aminergic GPCRs, we here present the development of covalently binding molecular tools activating Gs-, Gi-, and Gq-coupled receptors. The covalent agonists are derived from the monoamine neurotransmitters noradrenaline, dopamine, serotonin, and histamine, and they were accessed using a general and versatile synthetic strategy. We demonstrate that the tool compounds presented herein display an efficient covalent binding mode and that the respective covalent ligand-receptor complexes activate G proteins comparable to the natural neurotransmitters. A crystal structure of the β2-adrenoreceptor in complex with a covalent noradrenaline analog and a conformationally selective antibody (nanobody) verified that these agonists can be used to facilitate crystallogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.