Kisspeptin-10 10mg Nasal Spray

Kisspeptin nasal spray supplies the decapeptide Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2, CAS 374675-21-5, molecular weight 1302.46, as a metered aqueous solution. The molecule has two independent degradation routes that each add exactly one dalton, and neither is visible on a standard purity chromatogram.

Specification Table

Why Are the Degradation Routes Invisible?

This compound has a specific analytical problem that most peptides do not, and it is the most useful thing to know before buying a solution-state preparation.

The C-terminal amide is not decoration. It defines the RF-amide family and it is required for receptor binding. Lose it and the molecule becomes a carboxylic acid with sharply reduced affinity.

Amide hydrolysis replaces an amine with a hydroxyl, which changes the molecular weight from 1302.46 to roughly 1303.45. The difference is one dalton.

Separately, the asparagine residues at positions 2 and 4 deamidate to aspartate. That reaction also adds one dalton, and it is one of the most common spontaneous modifications in peptide chemistry.

So the molecule has three sites that each produce a plus-one mass shift. A low-resolution mass spectrometer reporting a nominal mass cannot distinguish 1302 from 1303.

Chromatographic separation of these species is possible but not guaranteed under a routine gradient, since the structural change is small and the retention shift can be minimal.

The practical consequence for kisspeptin nasal spray is that a preparation can degrade substantially at the position that matters most for receptor binding while continuing to pass a standard certificate of analysis.

One further wrinkle makes this harder than it first appears. Asparagine deamidation does not simply produce aspartate. It proceeds through a cyclic succinimide intermediate that opens to give either aspartate or isoaspartate.

Isoaspartate shifts the backbone by one carbon, which alters the peptide geometry substantially while leaving the mass identical to the aspartate form. Mass spectrometry cannot separate them at all.

Detecting isoaspartate requires a dedicated methyltransferase assay, which almost nobody runs on a commercial peptide. It is a real limit on what any certificate can tell you about this compound.

What Verification Actually Catches It?

The answer is more specific than asking for a higher purity number, and it is worth putting to a supplier directly.

High-resolution mass spectrometry resolves a one dalton difference comfortably, and the monoisotopic mass rather than the average mass is the figure that carries the information.

A certificate quoting a nominal or average mass to the nearest dalton has not answered the question. The instrument and the resolution both need to be stated.

Asking whether the method separates the amidated from the free-acid form is the direct version of the question, and a supplier who has considered it will have an answer.

Because deamidation accelerates in aqueous solution, the date of measurement matters as much as the number. A certificate from the manufacturing date describes material that no longer exists in an opened bottle.

The tyrosine and tryptophan give a genuine chromophore at 280 nanometres, so total peptide concentration is straightforward to measure even when the amide status is not.

That contrast is worth holding onto. Concentration here is easy and identity is hard. That is the reverse of the situation for most compounds in this catalogue.

What Does the Kiss1r Gpr54 Ligand Relationship Involve?

The receptor pairing is unusually well characterised for a compound in this catalogue, which makes the published numbers worth stating precisely.

The receptor was originally identified as an orphan G protein-coupled receptor designated GPR54 before its endogenous ligand was found, and it is now also designated KISS1R.

Published binding work reports a Ki of 2.33 nanomolar at the human receptor and 1.59 nanomolar at the rat receptor, which places this among the higher-affinity ligands in this range.

The parent protein is the product of the KISS1 gene, originally studied in the context of metastasis suppression. That is why the older literature uses the name metastin.

This decapeptide is the C-terminal fragment of that parent, and the fragment retains full receptor activity because the RF-amide motif at the carboxy terminus is the recognition element.

That structural fact is what makes the amide integrity question so consequential. The binding element and the labile group are the same chemical feature.

Longer forms including kisspeptin-54 exist and are separate compounds with their own registrations, so a citation needs to specify which length was used.

How Does 1302 Daltons Affect the Nasal Route?

This is the largest compound in the current spray batch, and size works against it on the variable that most reliably predicts transnasal transport.

Nasal absorption falls steeply with molecular weight, with the practical transition around 1,000 daltons where paracellular passage between epithelial cells becomes inefficient.

At 1302.46 daltons this compound sits above that transition, larger than Melanotan II at 1,024, Ipamorelin at 711.85 and Glutathione at 307.32.

Being above the threshold does not mean nothing crosses. It means the fraction is smaller and the variance between applications is wider, which raises the number of replicates an experiment needs.

The arginine gives a positive charge at physiological pH, and cationic molecules tend to bind a negatively charged mucosal surface rather than pass through it.

Published intranasal pharmacokinetic data for this compound is not established. The human clinical literature that does exist has used intravenous and subcutaneous routes.

Anyone designing around the nasal route for this molecule should handle delivered amount as an unknown to be measured rather than a parameter to be set.

What Kisspeptin Nasal Spray Dosage Figures Are Published?

Every figure below is an amount used in a published study, in the species and by the route that study used.

Human work has generally used intravenous infusion or subcutaneous injection, with amounts commonly expressed in picomoles or nanomoles per kilogram rather than in milligrams.

Rodent work spans a wider range and includes central administration. That is not comparable with any peripheral route and should not be converted.

Intranasal figures for this compound are not established in the peer-reviewed record, so no conversion from the intravenous literature can be made honestly without a measured absorption fraction.

Interspecies conversion requires allometric scaling by body surface area rather than body-weight arithmetic.

The spray format adds variables the vial does not, since metered volume, concentration, plume geometry and drainage all sit between an actuation and a deposited amount.

None of these figures is a recommendation. They are reference points from published studies conducted under conditions that may not resemble a given experiment.

What Does the RF-Amide Family Membership Imply?

The compound belongs to a defined structural family, and that membership carries information beyond nomenclature.

RF-amide peptides are named for a shared carboxy-terminal Arg-Phe-NH2 motif, and that motif is the receptor recognition element across the family rather than an incidental feature.

Several distinct RF-amide peptides exist in mammals, acting at different receptors, and they share the terminal motif while differing upstream.

For analysis that shared ending is a complication, since fragment ions from the carboxy-terminal region are not diagnostic between family members and identification has to rest on the upstream sequence.

For biology it means cross-reactivity is a question worth asking rather than dismissing, particularly in assays using antibodies raised against the conserved terminus.

It also explains why the amide is so consequential here. In a family where the terminal motif is the recognition element, losing the amide is not a minor modification.

Any antibody-based quantification of this compound should therefore be checked for what else it recognises, and any published measurement should state the antibody used.

The structural family is well defined in the literature, so this is a question with an answer rather than an open uncertainty.

How Should the Spray Be Stored and Recorded?

Storage advice for kisspeptin nasal spray is unusually consequential because the principal degradation route is silent.

Store between 2 and 8 degrees Celsius in the dark, and keep it out of the freezer, because freeze-thaw concentrates solutes at the ice boundary.

Deamidation is pH sensitive and accelerates under alkaline conditions, so a solution drifting upward in pH degrades faster at exactly the residues that matter.

The tryptophan at position 3 is photolabile and oxidation-prone, which is the second reason light protection is worth taking seriously here.

Because the failure mode produces no visible change and no reliable chromatographic signal, time in solution is the variable to control. Date the bottle when opened, and let that date count as part of the sample identity.

Record the lot, the stated concentration, the 280 nanometre reading if available, the date first opened, the storage temperature and the actuation count.

For a study spanning more than a few weeks, re-measuring rather than assuming is the only defensible approach with this molecule.

Published Literature

Selected references verified against the publisher record.

1. (‘Kotani M, Detheux M, Vandenbogaerde A, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276(37):34631-34636.’, ‘https://doi.org/10.1074/jbc.M104847200’)
2. (‘Ohtaki T, Shintani Y, Honda S, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411(6837):613-617.’, ‘https://doi.org/10.1038/35079135’)
3. (‘Dhillo WS, Chaudhri OB, Patterson M, et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005;90(12):6609-6615.’, ‘https://doi.org/10.1210/jc.2005-1468’)
4. (‘Robinson NE, Robinson AB. Molecular clocks. Proc Natl Acad Sci USA. 2001;98(3):944-949.’, ‘https://doi.org/10.1073/pnas.98.3.944’)

Frequently Asked Questions