title: Design, synthesis, and pharmacological characterization of fluorescent peptides for imaging human V1b vasopressin or oxytocin receptors.
abstract: Among the four known vasopressin and oxytocin receptors, the specific localization of the V1b isoform is poorly described because of the lack of selective pharmacological tools. In an attempt to address this need, we decided to design, synthesize, and characterize fluorescent selective V1b analogues. Starting with the selective V1b agonist [deamino-Cys(1),Leu(4),Lys(8)]vasopressin (d[Leu(4),Lys(8)]VP) synthesized earlier, we added blue, green, or red fluorophores to the lysine residue at position 8 either directly or by the use of linkers of different lengths. Among the nine analogues synthesized, two exhibited very promising properties. These are d[Leu(4),Lys(Alexa 647)(8)]VP (3) and d[Leu(4),Lys(11-aminoundecanoyl-Alexa 647)(8)]VP (9). They remained full V1b agonists with nanomolar affinity and specifically decorated the plasma membrane of CHO cells stably transfected with the human V1b receptor. These new selective fluorescent peptides will allow the cellular localization of V1b or OT receptor isoforms in native tissues.
authors.affiliation: Institute of Functional Genomics, CNRS UMR5203- INSERM U661, University of Montpellier I and II, Montpellier, France.
authors.forename: Maithé
authors.initials: M
authors.lastname: Corbani
authors.forename: Miguel
authors.initials: M
authors.lastname: Trueba
authors.forename: Stoytcho
authors.initials: S
authors.lastname: Stoev
authors.forename: Brigitte
authors.initials: B
authors.lastname: Murat
authors.forename: Julie
authors.initials: J
authors.lastname: Mion
authors.forename: Véra
authors.initials: V
authors.lastname: Boulay
authors.forename: Gilles
authors.initials: G
authors.lastname: Guillon
authors.forename: Maurice
authors.initials: M
authors.lastname: Manning
mesh_terms: D015195:Drug Design; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018045:Receptors, Oxytocin / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D010455:Peptides; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin