title: Structure-activity relationship study on small peptidic GPR54 agonists.
abstract: Metastin (kisspeptin-54) is an endogenous ligand that modulates gonadotropin-releasing hormone (GnRH) secretion through the interaction with a G protein-coupled receptor (GPCR), GPR54. The short-chain C-terminal decapeptide amide, metastin (45-54) (kisspeptin-10), exerts the identical bioactivities to metastin, such as metastasis suppression of cancer cells and inhibition of trophoblast migration and invasion. In order to understand the structural requirement for GPR54 agonistic activity, structure-activity relationship (SAR) study on pentapeptide-based C-terminal metastin analogues was carried out. As a result, H-Amb-Nal(2)-Gly-Leu-Arg-Trp-NH2 34 was identified as a novel GPR54 agonist that possessed the most potent GPR54 agonistic activity reported so far.
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: Ayumu
authors.initials: A
authors.lastname: Niida
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cluzeau
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: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: D000478:Alkylation; D000577:Amides / Q000737:chemistry; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006834:Hydrazines / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D006834:Hydrazines; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; C029424:hydrazine