title: SAR and QSAR studies on the N-terminally acylated pentapeptide agonists for GPR54.
abstract: Kisspeptins (KPs) play important roles in the regulation of physiological and pathological states through activation of the cognate receptor GPR54. Our previous studies to downsize KP agonists to the essential GPR54 pharmacophore identified peptides 1-3 as low molecular weight GPR54 agonists. In this study, the effect of N-terminal acyl groups on the activity of a series of analogues (R-Phe-Gly-Leu-Arg-Trp-NH2) was investigated in order to develop novel potent GPR54 agonists. Among the compounds developed, the most potent agonistic activity for GPR54 was observed for N-terminal 4-fluorobenzoyl analogue 29. Using quantitative structure-activity relationship studies, it was demonstrated that the inductively negative and small substituents were preferred at the 4-position of N-terminal benzoyl groups.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tomita
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cluzeau
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Navenot
authors.forename: Zi-xuan
authors.initials: ZX
authors.lastname: Wang
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Peiper
authors.forename: Miki
authors.initials: M
authors.lastname: Akamatsu
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: D000215:Acylation; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D008958:Models, Molecular; D009842:Oligopeptides / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D000074502:Receptors, Kisspeptin-1; D013329:Structure-Activity Relationship
chemical_list: C118688:KISS1R protein, human; D009842:Oligopeptides; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1