title: Structure-activity relationships of a series of analogues of the RFamide-related peptide 26RFa.
abstract: 26RFa is a new member of the RFamide peptide family that has been identified as the endogenous ligand of the orphan GPCR GPR103. As the C-terminal heptapeptide (26RFa((20-26))) mimics the action of the native peptide on food intake and gonadotropin secretion in rodents, we have synthesized a series of analogues of 26RFa((20-26)) and measured their potency to induce [Ca(2+)](i) mobilization in Gα(16)-hGPR103-transfected CHO cells. Systematic replacement of each residue by an alanine (Ala scan) and its D-enantiomer (D scan) showed that the last three C-terminal residues were very sensitive to the substitutions while position 23 tolerated rather well both modifications. Most importantly, replacement of Ser(23) by a norvaline led to an analogue, [Nva(23)]26RFa((20-26)), that was 3-fold more potent than the native heptapeptide. These new pharmacological data, by providing the first information regarding the structure-activity relationships of 26RFa analogues, should prove useful for the rational design of potent GPR103 receptor ligands with potential therapeutic application.
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, European Institute for Peptide Research (IFRMP 23), Cell Imaging Platform (PRIMACEN), University of Rouen, 76821 Mont-Saint-Aignan, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Le Marec
authors.forename: Cindy
authors.initials: C
authors.lastname: Neveu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lefranc
authors.forename: Christophe
authors.initials: C
authors.lastname: Dubessy
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Do-Régo
authors.forename: Jean
authors.initials: J
authors.lastname: Costentin
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Tonon
authors.forename: Manuel
authors.initials: M
authors.lastname: Tena-Sempere
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D008024:Ligands; D009479:Neuropeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D044387:GTP-Binding Protein beta Subunits; D008024:Ligands; D009479:Neuropeptides; C476582:QRFPR protein, human; D043562:Receptors, G-Protein-Coupled; C480638:prepro-26RFa protein, human; C058047:arginylphenylalaninamide; D002118:Calcium