Receptor–Ligand Interaction Measured by Inductively Coupled Plasma Mass Spectrometry and Selenium Labeling
| Autor: | Nolween Prache, Jean Martinez, Gilles Subra, Sonia Cantel, Carine Arnaudguilhem, Clémence Cheignon, Christine Enjalbal, Brice Bouyssiere, Emmanuelle Cordeau |
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| Přispěvatelé: | Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Vasopressins chemistry.chemical_element Peptide Plasma protein binding CHO Cells 010402 general chemistry Mass spectrometry Ligands 01 natural sciences Mass Spectrometry 03 medical and health sciences Selenium Cricetulus [CHIM.ANAL]Chemical Sciences/Analytical chemistry Drug Discovery Animals Receptor Inductively coupled plasma mass spectrometry G protein-coupled receptor chemistry.chemical_classification Chromatography Chemistry [CHIM.MATE]Chemical Sciences/Material chemistry Ligand (biochemistry) Receptor Cholecystokinin B 0104 chemical sciences [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry 030104 developmental biology [CHIM.POLY]Chemical Sciences/Polymers Isotope Labeling Molecular Medicine Peptides Protein Binding |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, American Chemical Society, 2018, 61 (22), pp.10173-10184. ⟨10.1021/acs.jmedchem.8b01320⟩ |
| ISSN: | 0022-2623 1520-4804 |
| Popis: | International audience; In the search for an alternative strategy to the radioactivity measurement conventionally performed to probe receptor–ligand interactions in pharmacological assays, we demonstrated that selenium labeling of the studied ligand combined with elemental mass spectrometry was as efficient and robust as the reference method but devoid of its environmental and health hazards. The proof-of-concept was illustrated on two GPCR receptors, vasopressin (V1A) and cholecystokinin B (CCK-B), involving peptides as endogenous ligands. We proposed several methodologies to produce selenium-labeled ligands according to peptide sequences along with binding affinity constraints. A selection of selenopeptides that kept high affinities toward the targeted receptor were engaged in saturation and competitive binding experiments with subsequent sensitive RP-LC-ICP-MS measurements. Experimental values of affinity constant (Ki) were perfectly correlated to literature data, illustrating the general great potency of replacing radioactive iodine by selenium for ligand labeling to further undergo unaffected pharmacology experiments efficiently monitored by elemental mass spectrometry. |
| Databáze: | OpenAIRE |
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