Kisspeptin-10 is the C-terminal decapeptide common to all the kisspeptins, the family of RFamide peptides processed from the KISS1 gene product. It is the endogenous agonist of the G protein-coupled receptor KISS1R (also called GPR54) and is used as a reference ligand in receptor binding, calcium mobilisation and kinase signalling assays. NuVion supplies kisspeptin as a synthetic peptide and laboratory chemical for in vitro research use only.
Key facts
| Type | Synthetic RFamide peptide, KISS1R agonist |
| Amino acid count | 10, C-terminally amidated |
| Sequence | Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 |
| Molecular formula | C63H83N17O14 |
| Molecular weight | 1302.4 g/mol |
| CAS number | 374675-21-5 |
| Synonyms | Kisspeptin-10, KP-10, metastin (45-54), KiSS-1 (112-121) |
| Supplied form | Lyophilised powder in a sealed vial |
Kisspeptin
$89 AUD
View productResearch use only. Not for human or veterinary use.
Structure and chemistry
The KISS1 gene encodes a 145-residue precursor that is cleaved into kisspeptin-54 (originally named metastin), with shorter products of 14, 13 and 10 residues arising from further processing. All of them share the same amidated C-terminus, and kisspeptin-10 corresponds to residues 112 to 121 of the precursor. The C-terminal Arg-Phe-NH2 places kisspeptin in the RFamide peptide family alongside neuropeptide FF, prolactin-releasing peptide and the RFRP peptides, which is why cross-reactivity at the NPFF receptors is checked when kisspeptin-10 is used at high concentration.
Kisspeptin-10 is the shortest fragment that retains full agonist activity at KISS1R. The C-terminal amide is required for receptor recognition, and the pentapeptide Phe-Gly-Leu-Arg-Phe-NH2 on its own still binds and activates the receptor, though with lower affinity. The peptide contains no cysteine and no disulfide, and it carries four aromatic side chains (Tyr1, Trp3, Phe6, Phe10). The N-terminal tyrosine is the site used for radioiodination when a labelled tracer is needed for binding studies. The human sequence ends in Phe, while the sequence in several other mammalian species ends in Tyr, so species matters when comparing literature values.
Two chemical liabilities are relevant to handling. The asparagine residues at positions 2 and 4 are susceptible to deamidation, and the tryptophan is susceptible to oxidation, both of which are accelerated by prolonged storage in solution, exposure to light, and alkaline pH. The Gly-Leu bond within the C-terminal motif is also cleaved by matrix metalloproteinases and neprilysin, so kisspeptin-10 has a short lifetime in serum-containing culture medium. Substituted analogues, including the KISS1R antagonist known as peptide 234, were designed around this fragment.
Mechanism of action
KISS1R is a class A G protein-coupled receptor that couples to Gq/11. Agonist binding activates phospholipase C beta, which hydrolyses phosphatidylinositol 4,5-bisphosphate to inositol trisphosphate and diacylglycerol. Inositol trisphosphate releases calcium from the endoplasmic reticulum, and diacylglycerol activates protein kinase C. In transfected CHO and HEK293 cells the response is measured as a rapid, transient rise in cytosolic calcium or as accumulation of inositol phosphates, with kisspeptin-10 acting at nanomolar concentrations and with a potency close to that of kisspeptin-54.
Downstream of the calcium and PKC signals, KISS1R activation drives phosphorylation of ERK1/2 and p38 MAP kinases and release of arachidonic acid through phospholipase A2. The receptor also recruits beta-arrestin, which contributes to ERK signalling and to receptor internalisation; in cell lines KISS1R desensitises relatively slowly compared with many other Gq-coupled receptors, and sustained agonist exposure leads to downregulation of surface receptor. In GnRH-expressing hypothalamic neurons and neuronal cell lines, the same Gq cascade closes inwardly rectifying potassium channels and opens TRPC-type cation channels, which depolarises the cell and increases firing and GnRH release at the cellular level. In other KISS1R-expressing cell lines, the receptor modulates focal adhesion signalling and reduces motility in migration and invasion assays, reflecting the context in which the gene was first identified.
Research applications
- Reference agonist for KISS1R in calcium mobilisation (fluorescent dye or aequorin) and IP1 accumulation assays in stably transfected CHO or HEK293 cells.
- Competition ligand in radioligand binding studies with iodinated kisspeptin, and for defining the pharmacology of KISS1R antagonists and biased analogues.
- ERK1/2 and p38 phosphorylation, beta-arrestin recruitment and receptor internalisation assays used to map KISS1R signalling and desensitisation.
- Electrophysiology and GnRH secretion measurements in GnRH-expressing neuronal cell lines and in KISS1R-transfected cells.
- Cell migration and invasion assays in KISS1R-expressing cell lines, and structure-activity work on RFamide ligands.
- RP-HPLC and LC-MS method development, including deamidation and oxidation stability studies of short amidated peptides.
Kisspeptin sits in NuVion’s Reproductive Signalling category with other neuropeptide and GPCR ligands.
Handling in the laboratory
Kisspeptin-10 is supplied lyophilised and is reconstituted with bacteriostatic water added slowly down the wall of the vial, then swirled until dissolved. The reconstitution calculator converts vial content and diluent volume into a stock concentration. The peptide is moderately hydrophobic because of its aromatic residues and dissolves readily at the concentrations used for stock solutions; if a stock is to be diluted into cell culture medium, the benzyl alcohol carried over should be accounted for with a vehicle control.
Unopened vials are kept sealed, dry, away from light and refrigerated as stated on the product documentation. Reconstituted solution is refrigerated, protected from light and used within the period given on the documentation; for longer holding it is divided into single-use aliquots and frozen, avoiding repeated freeze-thaw cycles. The compound is characterised by RP-HPLC for purity and by mass spectrometry for identity, and the deamidation products separate from the parent peak on a standard C18 gradient.
Testing and supply from NuVion
NuVion’s kisspeptin is manufactured at a GMP-audited facility and independently tested by Janoshik Analytical, with purity determined by RP-HPLC and identity confirmed by mass spectrometry. Most batches are tested, and the Certificate of Analysis for a tested batch is published on the product page and in the COA library. The peptide is supplied lyophilised in sealed vials and dispatched from within Australia.
Related compounds
Other Gq-coupled and neuropeptide receptor ligands in the same category include oxytocin, a cyclic nonapeptide acting at OXTR, and PT-141, a cyclic melanocortin analogue with MC4R and MC3R activity. The decapeptide it drives, synthetic gonadorelin, is covered separately.
Frequently asked questions
What is kisspeptin used for in research?
Kisspeptin-10 is the standard agonist for characterising KISS1R. It is used to calibrate calcium and inositol phosphate assays, as the competing ligand in binding studies, and as the stimulus in ERK phosphorylation, arrestin recruitment and GnRH secretion experiments in cell lines.
Which kisspeptin does NuVion supply?
The human kisspeptin-10 decapeptide, Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2, corresponding to residues 112 to 121 of the KISS1 precursor and to metastin (45-54). It is supplied as a lyophilised powder in a sealed vial with a published Certificate of Analysis.
Is kisspeptin a therapeutic good in Australia?
No. NuVion’s kisspeptin is a laboratory chemical for in vitro research. It is not included in the Australian Register of Therapeutic Goods, has not been assessed by the Therapeutic Goods Administration, and is not for human or veterinary use.
How should kisspeptin be stored?
Lyophilised vials are kept sealed, dry, protected from light and refrigerated per the product documentation. Once reconstituted, the solution is kept refrigerated and used within the stated period, or aliquoted and frozen. Solutions are kept at neutral or mildly acidic pH to limit deamidation of the two asparagine residues.
Research use only. This product is a laboratory chemical supplied for in vitro research. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. It is not for human or veterinary use, and nothing on this page is a representation about therapeutic use.
