title: Development of sub-nanomolar dipeptidic ligands of neuropeptide FF receptors.
abstract: Based on our earlier reported neuropeptide FF receptors antagonist (RF9), we carried out an extensive structural exploration of the N-terminus part of the amidated dipeptide Arg-Phe-NH(2) in order to establish a structure-activity relationships (SAR) study towards both NPFF receptor subtypes. This SAR led to the discovery of dipeptides (12, 35) with subnanomolar affinities towards NPFF1 receptor subtype, similar to endogenous ligand NPVF. More particularly, compound 12 exhibited a potent in vivo preventive effect on opioid-induced hyperalgesia at low dose. The significant selectivity of 12 toward NPFF1-R indicates that this receptor subtype may play a critical role in the anti-opioid activity of NPFF-like peptides.
authors.affiliation: University of Strasbourg, CNRS, UMR7200, Faculty of Pharmacy, F-67400 Illkirch Graffenstaden, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Gealageas
authors.forename: Séverine
authors.initials: S
authors.lastname: Schneider
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Humbert
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bertin
authors.forename: Martine
authors.initials: M
authors.lastname: Schmitt
authors.forename: Emilie
authors.initials: E
authors.lastname: Laboureyras
authors.forename: Christophe
authors.initials: C
authors.lastname: Dugave
authors.forename: Catherine
authors.initials: C
authors.lastname: Mollereau
authors.forename: Guy
authors.initials: G
authors.lastname: Simonnet
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Bourguignon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Simonin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bihel
mesh_terms: D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor