KPV is the tripeptide Lys-Pro-Val, the C-terminal fragment (residues 11 to 13) of alpha-melanocyte-stimulating hormone (alpha-MSH). It is a small, water-soluble synthetic peptide used in cell-based studies of NF-κB signalling, in transport studies on the oligopeptide transporter PepT1, and in in vitro antimicrobial assays. NuVion supplies KPV as a laboratory chemical for in vitro research use only.
Key facts
| Type | Synthetic tripeptide, C-terminal fragment of alpha-MSH |
| Amino acid count | 3 |
| Sequence | H-Lys-Pro-Val-OH |
| Molecular formula | C16H30N4O4 |
| Molecular weight | 342.4 g/mol |
| CAS number | 67727-97-3 |
| Synonyms | alpha-MSH(11-13), ACTH(11-13), Lys-Pro-Val |
| Supplied form | Lyophilised powder in a sealed vial |
Structure and chemistry
Alpha-MSH is a 13-residue peptide cut from proopiomelanocortin (POMC) by prohormone convertases and then N-terminally acetylated and C-terminally amidated. Its sequence is Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. The first 13 residues of ACTH are the same sequence, which is why the tripeptide is also labelled ACTH(11-13). KPV is the last three residues. The research compound is made by solid-phase synthesis with a free N-terminal amine and a free C-terminal carboxylic acid, so it differs from the amidated C-terminus of the parent hormone.
Four features of the sequence shape how the compound behaves in an assay. The lysine at position 1 carries a primary epsilon-amine, so KPV has a net positive charge at neutral pH and dissolves readily in aqueous buffers. The proline at position 2 restricts backbone conformation and makes the Lys-Pro bond resistant to many aminopeptidases, which slows breakdown in serum-containing medium compared with an unconstrained tripeptide. The valine at position 3 contributes a branched hydrophobic side chain. The sequence contains no methionine, cysteine, tryptophan or tyrosine, so the peptide is not prone to oxidation and cannot be quantified by absorbance at 280 nm; quantification relies on 214 nm absorbance, a mass-based preparation or the certificate value.
KPV lacks the His-Phe-Arg-Trp motif (residues 6 to 9 of alpha-MSH) that forms the minimal pharmacophore for melanocortin receptor binding. That is the structural reason its activity in cell models is described as independent of melanocortin receptor signalling. A disulfide-linked dimer, (CKPV)2, with a cysteine added at the N-terminus of each KPV unit, has also been synthesised for antimicrobial assay work.
Mechanism of action
The best-characterised activity of KPV in cell culture is inhibition of NF-κB signalling. In resting cells, NF-κB dimers containing the p65 (RelA) subunit are held in the cytoplasm by IκB proteins. Stimulation with TNF-α or IL-1β activates the IκB kinase complex, IκBα is phosphorylated and degraded, and the p65-containing dimer is carried into the nucleus by importin-α/β, where it drives transcription of genes such as IL8, IL6 and TNF. In human bronchial epithelial cells, KPV reduces the nuclear accumulation of p65 after cytokine stimulation, and the proposed site of action is downstream of IκBα degradation at the importin-dependent import step. Imaging of fluorescently tagged p65 shows the subunit staying cytoplasmic in KPV-exposed cells, and reporter-gene readouts show a matching fall in NF-κB-dependent transcription. In colonic epithelial lines (Caco-2 BBE and HT29-Cl.19A) and in Jurkat T cells, KPV also reduces phosphorylation of MAP kinases and secretion of IL-8 after cytokine stimulation.
Uptake into the cell is transporter-mediated. KPV is a substrate for PepT1 (SLC15A1), the proton-coupled oligopeptide transporter that carries di- and tripeptides across the apical membrane of intestinal epithelial cells and is also expressed in Jurkat cells and other immune cell lines. PepT1 uses the inward proton gradient to drive uptake, so transport is pH-dependent and is competed by other substrates such as glycyl-sarcosine. In PepT1-expressing cell lines, intracellular accumulation of KPV and its dampening of MAP kinase and NF-κB activation both depend on transporter activity; silencing PepT1 or competing the transporter removes the response. This ties the NF-κB observation to an intracellular site of action.
Alpha-MSH itself signals through the melanocortin receptors, chiefly MC1R on melanocytes and monocytes, which couple to Gs and raise cAMP. KPV lacks the receptor-binding core, does not act as a melanocortin receptor agonist in the conventional sense, and its activity in cell models is attributed to the intracellular mechanism described above. This makes KPV a useful comparator for alpha-MSH in experiments designed to separate receptor-dependent and receptor-independent actions of melanocortin peptides.
In microbiology assays, alpha-MSH and KPV reduce the viability of Staphylococcus aureus and Candida albicans in culture, and the dimer (CKPV)2 retains this activity. The antimicrobial mechanism is not fully defined; it does not depend on the melanocortin pharmacophore, since the tripeptide alone is active.
Research applications
KPV sits in NuVion’s Immune Signalling category. Typical study contexts include:
- NF-κB luciferase reporter assays in epithelial cell lines stimulated with TNF-α or IL-1β, with and without KPV
- p65 nuclear translocation studies by immunofluorescence, live imaging of tagged p65, or Western blotting of nuclear and cytoplasmic fractions
- Cytokine secretion assays (IL-8, IL-6, TNF-α by ELISA) and MAP kinase phosphorylation blots in Caco-2, HT-29 and Jurkat cells
- PepT1 transport work: uptake in PepT1-expressing versus non-expressing cells, competition with glycyl-sarcosine, pH dependence and siRNA knockdown
- Antimicrobial viability and MIC assays against S. aureus and C. albicans, comparing alpha-MSH, KPV and (CKPV)2
- Model tripeptide for peptide loading and release kinetics in hydrogel and polymer matrix studies, and for RP-HPLC method development on short hydrophilic peptides
Handling in the laboratory
KPV is supplied as a lyophilised powder in a sealed vial. Reconstitute with bacteriostatic water; the volume needed for a given working concentration can be worked out with the reconstitution calculator. The tripeptide dissolves with gentle swirling and does not need vortexing. Keep the unopened vial sealed, dry and away from light, refrigerated as stated in the product documentation. Once reconstituted, keep the solution refrigerated and use it within the period given on the documentation. If the work needs repeated sampling over a longer period, divide the solution into single-use aliquots to avoid freeze-thaw cycles. The compound is characterised by RP-HPLC for purity and by mass spectrometry for identity.
Testing and supply from NuVion
KPV from NuVion comes from GMP-audited manufacture and is independently tested by Janoshik Analytical. Most batches are tested, and the Certificate of Analysis for a tested batch, showing RP-HPLC purity and mass spectrometry identity, is published on the KPV product page and in the certificates of analysis library. The product is supplied lyophilised in sealed vials and dispatched from within Australia.
Related compounds
KPV is one of the four peptides in the KLOW blend, alongside GHK-Cu, BPC-157 and TB-500, where it supplies the melanocortin-derived input into NF-κB transcription. Other compounds in the same category include Thymosin Alpha-1, a 28-residue acetylated peptide studied in Toll-like receptor signalling, and LL-37, a 37-residue cathelicidin fragment used in membrane interaction and antimicrobial assays.
Frequently asked questions
What is KPV used for in research?
KPV is used as a tool compound in cell-based studies of NF-κB signalling, particularly the nuclear import of p65, and as a substrate in PepT1 transport assays. It also appears in in vitro antimicrobial work against S. aureus and C. albicans, and as a model tripeptide in hydrogel release and chromatography method development.
How does KPV differ from alpha-MSH?
Alpha-MSH is 13 residues long, acetylated and amidated, and activates melanocortin receptors through its His-Phe-Arg-Trp core. KPV is the last three residues only, lacks that core and is not a melanocortin receptor agonist. Its activity in cell culture is attributed to intracellular action after transporter-mediated uptake.
Is KPV a therapeutic good in Australia?
No. NuVion supplies KPV as a laboratory chemical for in vitro research, and it is not for human or veterinary use. The regulatory statement is set out in the research use only notice at the end of this article.
How should KPV be stored?
Keep the sealed vial of lyophilised powder dry, away from light and refrigerated as stated in the product documentation. After reconstitution with bacteriostatic water, refrigerate the solution and use it within the period on the documentation. Aliquot the solution if repeated sampling is planned, so that the stock is not put through freeze-thaw cycles.
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.
