Kisspeptin was found twice, in two unrelated fields, before anyone connected the findings. The name comes from the first one and the use comes from the second, which is a good reminder that a compound's name encodes its history and not its function.
Where the name comes from
KiSS-1 was identified as a metastasis suppressor gene. The peptides its product is cut into were later shown to be the natural ligands of GPR54, an orphan G protein-coupled receptor at the time. (Reference: Kotani et al., 2001) That finding joined two separate literatures.
Later work placed the kisspeptin-GPR54 system in the neuroendocrine control of reproduction, where it is now described as an upstream regulator of the axis. (Reference: Smith et al., 2006) Reviews of its role in the human axis followed. (Reference: Silveira et al., 2010)
Why the number 10
The gene product is processed into peptides of several lengths that share a C-terminal region. Kisspeptin-10 is the shortest of them, ten residues, and it is the fragment that carries the part the receptor reads.
The family works the way GHRH fragments do: a shorter chain retaining the active end. The practical consequence is identical, which is that "kisspeptin" on a label does not say which length is in the vial, and only a mass settles it.
The modification you cannot see in the sequence
The sequence is YNWNSFGLRF, and the C-terminus is amidated. That last detail is the interesting one for anyone checking a certificate.
Put YNWNSFGLRF into our molecular weight calculator and it returns C63H82N16O15 at 1303.45 g/mol. The catalogue figure is C63H83N17O14 at 1302.4, and the PubChem record agrees with the catalogue. Those two results differ by about one dalton and by one atom each of oxygen, nitrogen and hydrogen, which is exactly what amidation does: it replaces the terminal OH with NH2.
Neither figure is wrong. The calculator reports the free acid because a letter sequence contains no information about terminal modifications, a limit it shares with every sequence calculator. Knowing that is what stops a one-dalton difference from looking like a discrepancy, and it is why a certificate should say which species it measured.
Why the one-dalton lesson generalises
Terminal modifications are common in peptides built for research, and none of them appears in a letter sequence. Amidation at the C-terminus, acetylation at the N-terminus, a cyclising bond, a bound metal: each changes the mass and each is invisible to anything working from letters alone.
The practical rule that falls out is short. When a calculated mass and a certificate disagree by a small amount, check for a modification before concluding anything about the batch. When they disagree by a lot, the question is a different one. Our note on average versus monoisotopic mass covers the other common source of apparent disagreement.
Identity on paper
Kisspeptin-10 is C63H83N17O14, 1302.4 g/mol, CAS 374675-21-5. The number passes the check digit, which you can confirm with our validator, and resolves in PubChem to a record with a matching formula. Both steps, because the arithmetic never sees the compound name.
The sequence contains tryptophan and two phenylalanines, which is worth noting for a practical reason: tryptophan absorbs strongly at 280 nm, so this peptide is visible at a wavelength where many are not. Most peptide chromatography is run at 214 nm, where the peptide bond itself absorbs. Our note on HPLC covers why the detection wavelength belongs next to a purity figure.
What a certificate should show
Which length and which terminus. A document for this compound should state the ten-residue sequence and say the C-terminus is amidated, because without that the theoretical mass it reports cannot be checked against anything.
Then the usual: purity from RP-HPLC with conditions, identity from mass spectrometry with observed and theoretical mass, net peptide content stated separately from purity.
One impurity is specific to amidated peptides and worth asking about: incomplete amidation leaves free acid in the batch, differing from the target by one dalton. On a 1300-dalton molecule that is resolvable, but only if someone looked.
Ten residues, nine coupling steps
Short enough that synthesis is straightforward and deletion sequences are a smaller problem than on a long chain. That does not make the compound trivial, because the amidation is a separate step and the residue list includes one that complains. Tryptophan is the residue most likely to cause trouble, since its indole ring is sensitive to the acid conditions used in cleavage and deprotection, so a trace of modified tryptophan is a plausible impurity here in a way it is not on a sequence without it.
Storage
The usual routes apply and proceed with time and temperature. (Reference: Manning et al., 2010) This sequence has two asparagines, the residue most prone to deamidation, and deamidation converts an amide to an acid with a mass change of about one dalton. That is the same size as the amidation difference, which is a good reason for a certificate to state what it measured and when.
Our note on storage sets out the chemistry. The date on the document is what lets you place a result in the material's life.
Research use only
All products sold by Codex Research are strictly for laboratory research and development. They are not for human or animal consumption and are not intended to diagnose, treat, cure, or prevent any disease.
The compound at Codex Research
Kisspeptin-10, 10 mg per vial · batch-verified, with its certificate of analysis.
Frequently asked questions
What is kisspeptin-10?
A ten-residue amidated peptide, sequence YNWNSFGLRF, derived from the KiSS-1 gene product. The kisspeptins were identified as the natural ligands of the receptor GPR54.
Why is it called kisspeptin?
KiSS-1 was identified as a metastasis suppressor gene, and the peptides its product is cut into were later shown to be the ligands of GPR54. The name comes from the cancer literature; the use comes from reproductive neuroendocrinology.
Why does a calculator give a different mass from the catalogue?
The calculator returns the free acid, C63H82N16O15 at 1303.45, because a letter sequence carries no information about terminal modifications. The amidated form is C63H83N17O14 at 1302.4, which is what the catalogue and PubChem report.
What does amidation change?
It replaces the terminal OH with NH2, removing one oxygen and adding a nitrogen and a hydrogen. The mass difference is about one dalton, which is enough to look like a discrepancy if you do not know it is there.
What impurity is specific to amidated peptides?
Incomplete amidation, which leaves free acid in the batch differing from the target by one dalton. On a 1300-dalton molecule that is resolvable, provided someone looked for it.
Why does the tryptophan matter?
Two reasons. It absorbs strongly at 280 nm, so this peptide is visible at a wavelength where many are not, and its indole ring is sensitive to the acid conditions used in cleavage, making modified tryptophan a plausible impurity.
References
- Kotani, M., et al. (2001). The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. Journal of Biological Chemistry, 276(37), 34631-34636.
- Smith, J.T., Clifton, D.K., & Steiner, R.A. (2006). Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling. Reproduction, 131(4), 623-630.
- Silveira, L.G., Latronico, A.C., & Seminara, S.B. (2010). Kisspeptin and clinical disorders. Frontiers of Hormone Research, 39, 132-142.
- Kisspeptin-10 compound summary (CID 25240297). PubChem, National Library of Medicine.
- Manning, M.C., Chou, D.K., Murphy, B.M., Payne, R.W., & Katayama, D.S. (2010). Stability of protein pharmaceuticals: an update. Pharmaceutical Research, 27(4), 544-575.
- Dong, M.W. (2006). Modern HPLC for Practicing Scientists. Wiley.