KPV 10mg

What is KPV ?

KPV is the tripeptide Lys-Pro-Val, residues 11 to 13 of alpha-MSH, supplied as a 10mg lyophilised powder. Its route into cells is the PepT1 transporter, not a melanocortin receptor.

KPV is L-lysyl-L-prolyl-L-valine, a free acid of 342.43 g/mol, also catalogued as alpha-MSH (11-13). It lacks the His-Phe-Arg-Trp core that melanocortin receptors recognise, so it does not act like the intact hormone. Dalmasso et al. (Gastroenterology, 2008) found that nanomolar KPV inhibited NF-κB and MAP kinase signalling and reduced pro-inflammatory cytokine secretion in human intestinal epithelial cells and Jurkat T cells. The effect depended on uptake through PepT1, a di- and tripeptide transporter.

KPV Research Applications

• Signalling assays : NF-κB reporter and MAP kinase work in Caco2-BBE and HT29-Cl.19A epithelial cells and Jurkat T cells (Dalmasso et al., 2008).
• PepT1 transport : KPV competes with radiolabelled PepT1 substrates, and [³H]KPV has been used to measure uptake kinetics.
• Murine colitis : DSS- and TNBS-induced colitis (Dalmasso et al., 2008) and CD45RB(hi) transfer colitis (Kannengiesser et al., 2008).
• MC1R independence : effects in DSS colitis persisted in mice lacking a functional MC1R, so they are at least partly MC1R-independent (Kannengiesser et al., 2008).

KPV is also a common model cargo in colon-targeted delivery research, including nanoparticles and hydrogels. The evidence base is preclinical throughout, and no human clinical trial of KPV has been published.

KPV vs alpha-MSH and (CKPV)₂

Alpha-MSH is a 13 residue acetylated, amidated hormone that activates MC1R to MC5R through its His-Phe-Arg-Trp core. KPV is its last three residues and lacks that core. Mandrika et al. (Biochem Pharmacol, 2001) found KPV did not compete for MC1 receptor binding in RAW 264.7 macrophages, even at 1 mM, and did not raise cAMP. It still inhibited NF-κB translocation and nitric oxide production, with potency close to alpha-MSH. (CKPV)₂ is a cysteine-linked dimer, a different molecule with its own literature, and its findings do not transfer to KPV.

The C-terminus differs too. Native alpha-MSH ends in valine amide, while research KPV is the free acid, about 1 Da heavier. Check which species a certificate describes.

Research Overview

KPV is the tripeptide L-lysyl-L-prolyl-L-valine, molecular formula C₁₆H₃₀N₄O₄, molecular weight 342.43 g/mol, CAS 64790-08-5. It corresponds to residues 11 to 13 of alpha-melanocyte-stimulating hormone, whose full sequence is Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂, so KPV is simply the C-terminal end of that hormone. It is searched as k.p.v, k p v, KPV peptide and alpha-MSH (11-13), all the same molecule. One structural fact governs how the compound should be read: KPV does not contain the His-Phe-Arg-Trp message core that melanocortin receptors recognise, so classical melanocortin receptor agonism is not the mechanism reported in the primary literature. Dalmasso and colleagues (Gastroenterology, 2008) found that nanomolar KPV inhibited NF-κB and MAP kinase signalling and reduced pro-inflammatory cytokine output in Caco2-BBE intestinal epithelial cells and in Jurkat T cells, and that the effect depended on PepT1 (SLC15A1), the proton-coupled di/tripeptide transporter. On that account KPV is carried into the cell and acts intracellularly rather than at a surface receptor. PepT1 is normally a small-intestinal transporter but is induced in colonic epithelium and in immune cells during inflammation, so the transporter that carries the tripeptide is upregulated in the same tissue where the inflammatory models are run, a self-targeting property frequently noted in the PepT1 literature. Kannengiesser and colleagues (Inflamm Bowel Dis, 2008) reported anti-inflammatory activity for the same melanocortin-derived tripeptide in murine models of inflammatory bowel disease. The honest evidence position is that KPV has no human clinical trials, and a large share of the recent literature is delivery engineering, nanoparticles and hydrogels, rather than new mechanism.

Storage and Reconstitution

Store the sealed 10mg vial at -20°C, dry and away from light. Keep reconstituted solution refrigerated at 2-8°C and freeze single-use aliquots for longer holding. Avoid repeated freeze-thaw cycles and repeated stopper punctures.

Vials are sold on their own, without bacteriostatic water for mixing or other supplies.

How to reconstitute and handle

Let the vial reach room temperature. Run bacteriostatic water slowly down the inside wall of the vial and swirl gently. KPV is highly water-soluble and gives a clear, colourless solution. A tripeptide holds no secondary structure, so shear is not the concern. Hydrolysis in standing solution is, so prepare only what the experiment needs and refrigerate promptly. Label the vial with the reconstitution date.

• Allow the vial to reach room temperature before opening so condensation does not settle on the powder.
• KPV is highly water-soluble and dissolves readily; the solution should be clear and colourless.
• Note that a tripeptide is too short to hold secondary structure, so the usual concerns about shear-induced unfolding do not apply. The practical liabilities are instead hydrolysis of the two peptide bonds in standing aqueous solution and, in cell work, degradation by aminopeptidases in serum-containing medium.
• Avoid repeated freeze-thaw cycles and repeated stopper punctures.
• Handle under aseptic conditions, swabbing the stopper of both the KPV vial and the bacteriostatic water vial with alcohol before every needle entry.
• For PepT1-dependent experiments remember that the transporter is proton-coupled, so extracellular pH and the presence of competing di- and tripeptides in the medium will both affect measured uptake.

For the full method, see the peptide reconstitution guide and the reconstitution calculator.

Research References

• PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation (Dalmasso et al., Gastroenterology, 2008)
• Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease (Kannengiesser et al., Inflamm Bowel Dis, 2008)
• Effects of melanocortin peptides on NF-kappaB DNA binding and nitric oxide production in RAW 264.7 cells, evidence for dual mechanisms of action (Mandrika et al., Biochem Pharmacol, 2001)

Published research on KPV is indexed on PubMed. See our full UK buyer's guide for KPV and UK buyer's guide for KPV CoA.