Effects of systematic N-terminus deletions and benzoylations of endogenous RF-amide peptides on NPFF1R, NPFF2R, GPR10, GPR54 and GPR103.
Fiche publication
Date publication
septembre 2015
Journal
Peptides
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SIMONIN Frédéric
Tous les auteurs :
Rouméas L, Humbert JP, Schneider S, Doebelin C, Bertin I, Schmitt M, Bourguignon JJ, Simonin F, Bihel F
Lien Pubmed
Résumé
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.
Mots clés
Amino Acid Sequence, Humans, Neuropeptides, chemistry, Receptors, G-Protein-Coupled, chemistry, Receptors, Neuropeptide, chemistry, Sequence Deletion
Référence
Peptides. 2015 Sep;71:156-61