title: Convenient Access to Fluorescent Probes by Chemoselective Acylation of Hydrazinopeptides: Application to the Synthesis of the First Far-Red Ligand for Apelin Receptor Imaging.
abstract: Herein, we develop a convenient method to facilitate the solution-phase fluorescent labelling of peptides based on the chemoselective acylation of α-hydrazinopeptides. This approach combines the advantages of using commercially available amine-reactive dyes and very mild conditions, which are fully compatible with the chemical sensitivity of the dyes. The usefulness of this approach was demonstrated by the labelling of apelin-13 peptide. Various fluorescent probes were readily synthesized, enabling the rapid optimization of their affinities for the apelin receptor. Thus, the first far-red fluorescent ligand with sub-nanomolar affinity for the apelin receptor was characterized and shown to track the receptor efficiently in living cells by fluorescence confocal microscopy.
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67401, Illkirch, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Margathe
authors.affiliation: Neuropeptides Centraux et Régulations Hydrique et Cardiovasculaire, UMR 7241/Inserm U1050, Centre Interdisciplinaire de Recherche en Biologie, Collège de France, 11 place Marcelin Berthelot, 75231, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Iturrioz
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67401, Illkirch, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Regenass
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67401, Illkirch, France.
authors.forename: Iuliia A
authors.identifier: http://orcid.org/0000-0002-7633-3691
authors.initials: IA
authors.lastname: Karpenko
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, UMR-CNRS 7213, Faculté de Pharmacie, 74 route du Rhin, 67401, Illkirch, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Humbert
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, UMR-CNRS 7213, Faculté de Pharmacie, 74 route du Rhin, 67401, Illkirch, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: de Rocquigny
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67401, Illkirch, France.
authors.forename: Marcel
authors.initials: M
authors.lastname: Hibert
authors.affiliation: Neuropeptides Centraux et Régulations Hydrique et Cardiovasculaire, UMR 7241/Inserm U1050, Centre Interdisciplinaire de Recherche en Biologie, Collège de France, 11 place Marcelin Berthelot, 75231, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Llorens-Cortes
authors.affiliation: Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS/Université de Strasbourg, Labex MEDALIS, Faculté de Pharmacie, 74 route du Rhin, 67401, Illkirch, France. dominique.bonnet@unistra.fr.
authors.forename: Dominique
authors.identifier: http://orcid.org/0000-0002-8252-9199
authors.initials: D
authors.lastname: Bonnet
mesh_terms: D000215:Acylation; D005456:Fluorescent Dyes / Q000737:chemistry*; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D006834:Hydrazines; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide
keywords: G-protein-coupled receptors; chemical ligation; fluorescent probes; hydrazinopeptides; receptors