title: Effects of systematic N-terminus deletions and benzoylations of endogenous RF-amide peptides on NPFF1R, NPFF2R, GPR10, GPR54 and GPR103.
abstract: Mammalian RF-amide peptides including RF-amide-related peptides-1 and -3, neuropeptides AF and FF, Prolactin releasing peptides, Kisspeptins and RFa peptides are currently considered endogenous peptides for the GPCRs NPFF1R, NPFF2R, GPR10, GPR54 and GPR103, respectively. While NPFF1R and NPFF2R displayed high affinity for all the RF-amide peptides, GPR10, GPR54 and GPR103 only bind their cognate ligands. Through a systematic and sequential N-terminus deletion and benzoylation of either RF-amide neuropeptide (RFRP-3, NPFF, Kp-10, PrRP20, and 26RFa), we report the corresponding impact on affinity and activity towards all the RF-amide receptors (NPFF1R, NPFF2R, GPR10, GPR54 and GPR103). Our results highlight the difficulty to develop selective peptide ligands for GPR10, GPR54 or GPR103 without a modification of the C-terminus RF-amide signature, but open the door to the design of new RF-amide peptides acting as agonist for one receptor and antagonist for another one.
authors.affiliation: University of Strasbourg, CNRS, UMR7200, Faculty of pharmacy, 67400 Illkirch Graffenstaden, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Rouméas
authors.affiliation: University of Strasbourg, CNRS, UMR7242, ESBS, 67412 Illkirch Graffenstaden, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Humbert
authors.affiliation: University of Strasbourg, CNRS, UMR7200, Faculty of pharmacy, 67400 Illkirch Graffenstaden, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Schneider
authors.affiliation: University of Strasbourg, CNRS, UMR7200, Faculty of pharmacy, 67400 Illkirch Graffenstaden, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Doebelin
authors.affiliation: University of Strasbourg, CNRS, UMR7242, ESBS, 67412 Illkirch Graffenstaden, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bertin
authors.affiliation: University of Strasbourg, CNRS, UMR7200, Faculty of pharmacy, 67400 Illkirch Graffenstaden, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: University of Strasbourg, CNRS, UMR7200, Faculty of pharmacy, 67400 Illkirch Graffenstaden, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Bourguignon
authors.affiliation: University of Strasbourg, CNRS, UMR7242, ESBS, 67412 Illkirch Graffenstaden, France. Electronic address: simonin@unistra.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Simonin
authors.affiliation: University of Strasbourg, CNRS, UMR7200, Faculty of pharmacy, 67400 Illkirch Graffenstaden, France. Electronic address: fbihel@unistra.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bihel
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D009479:Neuropeptides / Q000737:chemistry* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide / Q000737:chemistry* / Q000235:genetics; D017384:Sequence Deletion
chemical_list: C118688:KISS1R protein, human; D009479:Neuropeptides; C112345:PRLHR protein, human; C476582:QRFPR protein, human; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor
keywords: 26RFa; GPR10; GPR103; GPR54; Kisspeptin; NPFF; PrRP; RF-amides