Design synthesis and pharmacological characterization of fluorescent peptides for imaging human V1b vasopressin or oxytocin receptors

摘要

Among the four known vasopressin and oxytocin receptors, the specific localization of the V1b isoform is poorly described due to 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-Cys¹, Leu⁴, Lys⁸]vasopressin (d[Leu⁴,Lys⁸]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[Leu⁴, Lys (Alexa 647)⁸]VP >(3) and d[Leu⁴, 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 localisation of V1b or OT receptor isoforms in native tissues.