KPV is the three-amino-acid sequence lysine-proline-valine, corresponding to residues 11-13 of alpha-melanocyte-stimulating hormone (alpha-MSH), the tridecapeptide processed from proopiomelanocortin (POMC). In published research it is often written as alpha-MSH(11-13) or simply KPV. Laboratories study it as a minimal fragment that retains much of the signaling activity of the parent hormone in cell culture and rodent models of inflammation, independent of the pigment-related activity alpha-MSH carries through melanocortin receptors on melanocytes.
| Attribute | Detail |
|---|---|
| Name | KPV (Lys-Pro-Val), also written alpha-MSH(11-13) |
| Class | Tripeptide, C-terminal fragment of a melanocortin |
| Sequence length | 3 amino acids |
| Origin | C-terminal end of alpha-MSH, itself derived from POMC |
| What studies examine | NF-kB activation, pro-inflammatory cytokine expression, epithelial and macrophage models, rodent colitis and peritonitis models |
| Form supplied | Lyophilized powder, research use only |
What is the chemical structure of KPV?
KPV is a linear tripeptide built from three standard amino acids in sequence: lysine, proline, valine. It is the shortest fragment of alpha-MSH that researchers have characterized as retaining anti-inflammatory activity in cell and animal models. Because it is only three residues, it is structurally simple compared to full-length alpha-MSH, which is thirteen amino acids, or to larger melanocortin analogs used in other lines of research.
Where does KPV come from in alpha-MSH?
Alpha-MSH is produced from POMC, a precursor protein that is also the source of ACTH and other melanocortin peptides (UniProt entry for human POMC). The core melanocortin message sequence His-Phe-Arg-Trp sits in the middle of alpha-MSH, while KPV occupies the C-terminal end. Research groups have used this structure to test which part of the alpha-MSH molecule accounts for which activity, and KPV has repeatedly come up as the fragment associated with anti-inflammatory signaling in the studies below (Luger and Brzoska, 2007).
What have in vitro studies examined?
Cell-based studies of KPV cluster around three general areas: NF-kB signaling, cytokine output in immune and epithelial cell models, and intestinal epithelial cell lines specifically.
NF-kB signaling
In human bronchial epithelial cells (16HBE14o- and related lines), KPV was reported to suppress TNF-alpha-triggered NF-kB activity in a dose-dependent manner and to block nuclear import of the p65RelA subunit. The same study reported that KPV increased cellular IkB-alpha abundance during TNF-alpha exposure and competed with importin-alpha3 for binding to p65RelA in vitro, pointing to a nuclear-transport step as one candidate mechanism (Land, 2012).
Cytokine and macrophage models
Getting et al. (2003) compared KPV to full-length alpha-MSH and to melanocortin receptor agonists in macrophage activation assays. Alpha-MSH and the MC3/4-R agonist MTII reduced macrophage release of KC and IL-1beta and raised intracellular cAMP, but KPV did not raise cAMP in that assay and its anti-inflammatory effect in vivo was not blocked by a melanocortin receptor 3/4 antagonist, leading the authors to propose that KPV instead interferes with IL-1beta signaling.
Intestinal epithelial models
Dalmasso et al. (2008) examined KPV in human intestinal epithelial cell lines (Caco2-BBE, HT29-Cl.19A) and Jurkat T cells stimulated with pro-inflammatory cytokines. Using an NF-kB luciferase reporter, Western blot, RT-PCR and ELISA, the study reported that nanomolar concentrations of KPV inhibited NF-kB and MAP kinase signaling and reduced pro-inflammatory cytokine secretion in these lines. The same paper reported that KPV uptake occurred through PepT1, the di/tripeptide transporter expressed in the small intestine and induced in the colon during inflammatory bowel disease, using both competition assays against a radiolabelled PepT1 substrate and direct uptake measurements with tritiated KPV.
What have rodent studies examined?
Several rodent studies have looked at KPV in models of intestinal and peritoneal inflammation.
- Kannengiesser et al. (2008) studied KPV in dextran sodium sulfate (DSS) colitis and CD45RB(hi) transfer colitis in mice, tracking body weight, colon histology, and myeloperoxidase activity as markers of inflammation. The study also included mice expressing a nonfunctional melanocortin-1 receptor to test whether the effect required that receptor.
- Dalmasso et al. (2008) added KPV to the drinking water of mice with DSS- and TNBS-induced colitis and assessed histology and pro-inflammatory cytokine mRNA expression in colon tissue.
- Getting et al. (2003) studied KPV in a mouse model of crystal-induced peritonitis and in IL-1beta-induced peritonitis, measuring polymorphonuclear leukocyte accumulation in the peritoneal cavity, including in mice with a nonfunctional MC1-R.
These are laboratory models of disease in animals, not clinical studies in humans, and none of the compounds involved were administered as a therapeutic protocol in the sense of a prescribed human or veterinary treatment.
Is KPV's activity melanocortin-receptor dependent?
The literature on this point is mixed and still discussed. Getting et al. (2003) reported that KPV, unlike alpha-MSH and MC3/4-R agonists, did not raise cAMP in macrophage assays and that its anti-inflammatory effect in vivo was not blocked by a melanocortin receptor 3/4 antagonist, concluding KPV is "unlikely to mediate its effects through melanocortin receptors" in that model. Land (2012) described a mechanism centered on nuclear transport competition with importin-alpha3 rather than receptor binding at the cell surface. Luger et al. (2003), by contrast, reported that KPV was able to bind MC-1R and modulate antigen-presenting cell function in a contact hypersensitivity model. Taken together, the published studies describe more than one candidate pathway, and researchers examining KPV generally note that its activity does not map cleanly onto classic melanocortin receptor pharmacology the way full-length alpha-MSH does.
How does KPV differ from full-length alpha-MSH?
Alpha-MSH is a tridecapeptide with a central melanocortin message sequence that drives receptor binding and, through MC1R, effects on melanocytes. KPV is only the C-terminal three residues of that molecule. In the studies cited above, KPV was reported to retain anti-inflammatory signaling seen with alpha-MSH in several models while behaving differently in cAMP and receptor-antagonist assays, which is why researchers treat it as a distinct research tool rather than a shorthand for alpha-MSH itself.
Why does KPV appear in the KLOW blend?
KLOW is a combination research blend that pairs KPV with other peptides in Homegrown's blend lineup. The rationale researchers cite for including a short anti-inflammatory-signaling fragment like KPV alongside other peptides in a combination blend is covered in detail on the GLOW vs KLOW blend comparison, which breaks down what each blend contains and how the two differ. For background on KPV specifically and on the blend as supplied, see the KPV research monograph and the KLOW blend monograph.
Handling notes
KPV is supplied as a lyophilized powder for research use. Like other short peptides, it should be stored per the certificate of analysis and reconstituted using standard bench technique and concentration math; this is bench math for preparing a solution, not guidance for use in any subject; see peptide storage and stability for temperature, light and freeze-thaw considerations that apply to lyophilized and reconstituted peptides generally. As with any research peptide, researchers should confirm identity and purity from the lot-specific certificate of analysis before use in an assay, and handle it under normal laboratory practice for peptide reagents (clean glassware, appropriate PPE, and documented chain of custody for the material). Lot-specific specs and the current certificate of analysis for research-grade KPV are posted on our KPV lot page.
Frequently asked questions
Is KPV the same molecule as alpha-MSH?
No. KPV is a three-amino-acid fragment (residues 11-13) of the thirteen-amino-acid alpha-MSH molecule. Studies have looked at KPV specifically because it is a minimal fragment, not a synonym for the full peptide.
Does KPV activate melanocortin receptors the way alpha-MSH does?
Published studies do not agree on this point. Some report that KPV does not raise cAMP or depend on MC3/4-R signaling in the assays used, while another study reported KPV binding to MC-1R in a different model. Researchers cite this as an open question rather than a settled mechanism.
What is KdPT and how does it relate to KPV?
KdPT is a related tripeptide described in the literature as structurally connected to the C-terminal region relevant to alpha-MSH-derived research, studied separately in models of skin inflammation. It is a distinct sequence from KPV and is not the subject of this article.
Why is KPV studied alongside PepT1?
PepT1 is a di/tripeptide transporter normally expressed in the small intestine and reported to be induced in the colon during inflammatory bowel disease models. Dalmasso et al. (2008) reported that KPV uptake into intestinal epithelial and immune cells occurred through this transporter, which is why PepT1 comes up in papers studying KPV in intestinal models specifically.
What is the KLOW blend and why does it include KPV?
KLOW is a combination blend in Homegrown's product line that includes KPV alongside other peptides. The specific composition and how it compares to the related GLOW blend are covered in the GLOW vs KLOW comparison article.
How is KPV supplied for laboratory use?
As a lyophilized powder intended for research use only, sold by lot with an accompanying certificate of analysis, consistent with how other short research peptides on this site are supplied.
References
- Kannengiesser K, Maaser C, Heidemann J, et al.. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008. PubMed 18092346.
- Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al.. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008. PubMed 18061177.
- 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. PMC3403564.
- Luger TA, Brzoska T. alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Ann Rheum Dis. 2007. PubMed 17934097.
- Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J Pharmacol Exp Ther. 2003. PubMed 12750433.
- Luger TA, Scholzen TE, Brzoska T, et al.. New insights into the functions of alpha-MSH and related peptides in the immune system. Ann N Y Acad Sci. 2003. PubMed 12851308.
- UniProt Consortium. POMC - Proopiomelanocortin - Homo sapiens (human), entry P01189. UniProt P01189.
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
