Design and synthesis of downsized metastin (45-54) analogs with maintenance of high GPR54 agonistic activity.
Niida. Ayumu A; Wang. Zixuan Z; Tomita. Kenji K; Oishi. Shinya S; Tamamura. Hirokazu H; Otaka. Akira A; Navenot. Jean-Marc JM; Broach. James R JR; Peiper. Stephen C SC; Fujii. Nobutaka N
Key Findings
- Alanine and D‑amino acid scans pinpointed which parts of the peptide are crucial for receptor activation
- Shortened peptides (named 32, 33, and 39) with an N‑terminal basic group and a C‑terminal RW‑amide act as strong GPR54 agonists, comparable to the full‑length peptide
- The activity was demonstrated using a yeast system engineered to report GPR54 signaling
Practical Outcomes
- These findings are interesting for drug development but not actionable for biohackers. More research, safety testing, and human trials are needed before any dosing or protocol can be suggested.
Summary
Scientists created shorter versions of the kisspeptin-10 peptide that still activate its receptor in a yeast test, but there’s no human data or dosing information yet, so it isn’t ready for personal use.
Abstract
Metastin has been identified as a metastasis suppressor gene product that mediates its function through a G protein coupled receptor, GPR54. To refine insight into the critical pharmacophore for the activation of GPR54, we have conducted alanine and d-amino acid scanning on a biologically active metastin fragment (45-54). Based on these data and structures of peptides previously reported to activate GPR54, a series of shortened metastin (45-54) derivatives were synthesized and tested for the ability to induce GPR54 signaling. These biological experiments were performed in yeast containing human GPR54 that was coupled to the pheromone response pathway and a pheromone responsive lacZ reporter gene. Compounds 32, 33, and 39, which possess an N-terminal basic group and a C-terminal RW-amide motif, were strong agonists, similar to the level of metastin. This may provide an approach to reverse the pro-metastatic effect of metastin deletion in multiple malignant tumors.
Study Information
pubmed
2005
2005-10-18T00:00:00.000Z
10.1016/j.bmcl.2005.09.054