Structure-activity relationship study on small peptidic GPR54 agonists

Bioorg Med Chem. 2006 Nov 15;14(22):7595-603. doi: 10.1016/j.bmc.2006.07.009. Epub 2006 Aug 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Amides / chemistry
  • Animals
  • CHO Cells
  • Cricetinae
  • Hydrazines / chemistry
  • Molecular Structure
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / pharmacology*
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Structure-Activity Relationship


  • Amides
  • Hydrazines
  • Peptides
  • Receptors, G-Protein-Coupled
  • hydrazine