Structure-activity relationship study on small peptidic GPR54 agonists.
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.
Tomita
Kenji
K
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Niida
Ayumu
A
Oishi
Shinya
S
Ohno
Hiroaki
H
Cluzeau
Jérôme
J
Navenot
Jean-Marc
JM
Wang
Zi-xuan
ZX
Peiper
Stephen C
SC
Fujii
Nobutaka
N
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
D000577:Amides; D006834:Hydrazines; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; C029424:hydrazine