Lysine, Proline, Valine: How KPV Comes From Alpha-MSH
KPV is three amino acids long, and all three are borrowed: lysine, proline and valine are the final links of alpha-MSH, the hormone best known for its role in skin pigment. Four decades of research show that if you cut that hormone in the right place, the pigment signal stays behind and most of the anti-inflammatory activity travels with the tail. Here is the family line, from alpha-MSH to KPV, melanotan II and the unrelated GHK.
View product →Findings
- KPV is Lys-Pro-Val: positions 11 to 13 of alpha-MSH, a 13-amino-acid hormone cut from the precursor protein POMC.
- Pigment signalling runs through a core in the middle of the hormone, His-Phe-Arg-Trp. KPV contains none of it, and a 2010 review describes KPV as keeping almost all of the hormone’s anti-inflammatory capacity, with no pigment action.
- A 2008 study in Gastroenterology showed KPV is carried into gut and immune cells by the transporter PepT1, where nanomolar amounts damped NF-kB inflammatory signalling.
- Melanotan II is built from the other end of the hormone: positions 4 to 10, core included, KPV left out. GHK, the peptide in GHK-Cu, is a separate tripeptide (Gly-His-Lys) from human plasma.
Alpha-MSH, link by link
Alpha-melanocyte-stimulating hormone (alpha-MSH) is a chain of 13 amino acids cut from a larger precursor protein, proopiomelanocortin (POMC). The same precursor yields ACTH, whose opening stretch contains the full alpha-MSH sequence. In one-letter code the hormone reads SYSMEHFRWGKPV:
| Positions | Sequence | Role |
|---|---|---|
| 1 to 5 | Ser-Tyr-Ser-Met-Glu | Opening stretch |
| 6 to 9 | His-Phe-Arg-Trp | Receptor core; drives pigment via MC1R |
| 10 | Gly | Links core and tail |
| 11 to 13 | Lys-Pro-Val | KPV, the anti-inflammatory tail |
A 2008 review in Endocrine Reviews lists the hormone’s anti-inflammatory effects across fever, skin, gut, eye, brain and airway models, then names the obstacle: its pigmentary effect. So attention turned to the tail.
How the tail was found
The first clue came from fever research. In 1984 Richards and Lipton noted that alpha-MSH lowered fever while alpha-MSH (1 to 10), missing the last three amino acids, had no effect. Tested alone, lysine-proline-valine lowered fever too, pointing to the tail as part of the hormone’s active message. In 1989 Lipton’s group showed it reduced swelling in a contact-inflammation model, and proposed it as a template for new anti-inflammatory peptides.
In 2003 a team at the William Harvey Research Institute in London found that KPV cut white-cell influx in a model of peritonitis, but did not raise cAMP, the messenger melanocortin receptors use; a receptor-blocking compound did not stop it; and it still worked where MC1R was non-functional. The authors concluded KPV most likely works against IL-1 beta rather than through melanocortin receptors.
A 2010 review from the University of Münster summed it up: KPV lacks the entire motif needed to bind any known melanocortin receptor, yet retains almost all of the anti-inflammatory capacity of the full hormone, without any pigment action.
The gut research and PepT1
KPV’s best-known work is in the intestine. PepT1 carries di- and tripeptides into cells; it is found in the small intestine and switched on in the colon during inflammatory bowel disease.
- 2008, Emory University. In human intestinal epithelial cells and human T cells, nanomolar KPV inhibited NF-kB and MAP kinase signalling, with uptake running through PepT1. Given in drinking water, KPV reduced colitis in two laboratory models.
- 2008, University of Münster. In two colitis models, KPV brought earlier recovery and fewer inflammatory infiltrates, and still protected where MC1R was not working.
- 2010, colon-targeted delivery. Packed into nanoparticles inside a gel that opens in the colon, KPV matched the effect of free KPV at a concentration 12,000-fold lower.
In human bronchial epithelial cells, KPV entered the nucleus and blocked the import of p65, a subunit of NF-kB, lowering IL-8 and eotaxin secretion (Land, 2012).
The family tree: melanotan II and GHK
Melanotan II comes from the opposite end: a cyclic, lactam-bridged analogue of positions 4 to 10 that keeps the receptor core and drops the tail. In a 1996 pilot study in three healthy men, two showed increased skin pigmentation; the study also recorded arousal effects, the observation behind PT-141. Our melanotan II and PT-141 history covers that branch.
GHK, glycyl-histidyl-lysine, is a copper-binding tripeptide isolated from human plasma. In 1988, GHK-Cu stimulated collagen synthesis in fibroblast cultures, and the authors noted the GHK sequence also sits inside type I collagen, from which enzymes at a wound may release it. KPV and GHK share a lysine, at opposite ends, and nothing else. Why GHK-Cu is blue covers the copper side.
Reading a sequence for KPV
To place any melanocortin peptide, read its last three amino acids. If the chain ends in Lys-Pro-Val, it carries KPV: full alpha-MSH does, and so does any ACTH fragment long enough to reach position 13. If it stops at position 10, as melanotan II does, the KPV piece is gone. One close relative is KdPT (Lys-D-Pro-Thr), a KPV derivative matching amino acids 193 to 195 of the inflammatory messenger IL-1 beta. If Lys-Pro-Val is what you want to study, KPV supplies it on its own.
Where the research stands
The KPV work so far is laboratory research, in human cells and colitis models, and reviews from the Münster group point to bowel, skin and airway inflammation as the natural next targets for clinical study.
KPV in a vial, a spray or a blend
We supply KPV three ways. KPV comes as a lyophilised 10 mg vial, reconstituted with bacteriostatic water; the KPV reconstitution guide and peptide calculator cover the arithmetic. The KPV Nasal Spray arrives ready-mixed in a sealed metered atomiser, in 10 mg and 20 mg bottles, with no reconstitution step.
KPV is also one of the four peptides in KLOW, with GHK-Cu, BPC-157 and TB-500, so the blend carries both tripeptides discussed here. Choose the KLOW Blend vial or the ready-mixed KLOW Nasal Spray; KLOW vs GLOW explains the difference KPV makes.
KPV is supplied for laboratory research use only. For more, see KPV: the anti-inflammatory tripeptide, explained, our guide to buying KPV in Canada and the gut health research notes.
Frequently asked questions
What does KPV stand for?
The one-letter codes of its three amino acids: K for lysine, P for proline and V for valine. Together they are positions 11 to 13 of alpha-MSH.
Is KPV the same as alpha-MSH?
No. KPV is the last three of alpha-MSH’s 13 amino acids. It lacks the His-Phe-Arg-Trp receptor core, and reviews describe it as anti-inflammatory without the hormone’s pigment action.
Is KPV related to melanotan II?
Both trace back to alpha-MSH, from opposite ends. Melanotan II is a cyclic synthetic analogue of positions 4 to 10 and keeps the receptor core; KPV is positions 11 to 13 and does not.
How is KPV different from GHK-Cu?
GHK is a separate copper-binding tripeptide, glycyl-histidyl-lysine, isolated from human plasma, and its sequence also occurs in type I collagen. It is not part of alpha-MSH. The KLOW blend contains both.
Where can I buy KPV in Canada?
Vistara Labs supplies KPV as a 10 mg lyophilised vial, as a ready-mixed nasal spray in 10 mg and 20 mg sizes, and in the KLOW blend, shipped from within Canada. Laboratory research use only.
Sources: Richards DB, Lipton JM. Effect of alpha-MSH 11-13 (lysine-proline-valine) on fever in the rabbit. Peptides. 1984. PMID 6333677. Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH. FASEB J. 1989. PMID 2550304. Getting SJ et al. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J Pharmacol Exp Ther. 2003. PMID 12750433. Brzoska T et al. Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr Rev. 2008. PMID 18612139. Brzoska T et al. Terminal signal: anti-inflammatory effects of alpha-melanocyte-stimulating hormone related peptides beyond the pharmacophore. Adv Exp Med Biol. 2010. PMID 21222263. Dalmasso G et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008. PMID 18061177. Kannengiesser K et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008. PMID 18092346. Laroui H et al. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 2010. PMID 19909746. Land SC. Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists. Int J Physiol Pathophysiol Pharmacol. 2012. PMID 22837805. Dorr RT et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996. PMID 8637402. Maquart FX et al. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Lett. 1988. PMID 3169264.
References
No human exposure study of KPV was identified by any route. The foundational research below is cellular and animal work.
- PepT1-mediated tripeptide KPV uptake reduces intestinal inflammationLaboratory study in human intestinal epithelial cells and human T cells; no human exposure.
Links open the study record on PubMed so the source can be checked directly. Listing a study is not a claim that its findings apply to any other use, product or route of administration. Research use only.
