KPV

KPV is the tripeptide Lys-Pro-Val, corresponding to residues 11–13 at the C-terminus of alpha-melanocyte-stimulating hormone (α-MSH), a 13-residue product of proopiomelanocortin. α-MSH is best known for driving pigmentation through the melanocortin-1 receptor, but it also has well-documented anti-inflammatory and antipyretic activity. Work in the late 1980s traced the antipyretic and anti-inflammatory message of α-MSH to its C-terminal tripeptide: Hiltz and Lipton showed in 1989 that Lys-Pro-Val alone inhibited increases in vascular permeability and reduced inflammation in mice [1], and a follow-up study of stereoisomers found that L-proline at position 12 was essential for activity whereas the lysine was not, and that a D-valine substitution increased anti-inflammatory potency roughly four-fold [2]. Because KPV lacks the central His-Phe-Arg-Trp motif required for melanocortin-receptor-driven pigmentation, it has been proposed as an anti-inflammatory scaffold free of the melanogenic effect of the parent peptide [3].

Mechanism — NF-κB and PepT1

The clearest mechanistic study is Dalmasso and colleagues in Gastroenterology in 2008. In human intestinal epithelial cell lines (Caco2-BBE, HT29-Cl.19A) and Jurkat T cells stimulated with pro-inflammatory cytokines, nanomolar KPV inhibited NF-κB activation, measured by luciferase reporter, and MAP-kinase signalling, and reduced pro-inflammatory cytokine secretion. Competition and radiolabelled-uptake experiments showed that KPV enters cells through PepT1, the proton-coupled di/tripeptide transporter that is normally confined to the small intestine but is induced in the colon during inflammatory bowel disease [4]. This transporter-mediated route is notable because it means KPV activity in intestinal epithelium does not require a melanocortin receptor at all, a point reinforced by Kannengiesser and colleagues, who found that KPV remained effective in mice carrying a non-functional MC1 receptor [5].

Mouse colitis studies

In the Dalmasso study, KPV added to drinking water reduced the incidence and severity of both dextran sulfate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS) colitis in mice, with lower pro-inflammatory cytokine expression and less histological damage [4]. Kannengiesser and colleagues tested KPV in DSS colitis and in CD45RB-high T-cell transfer colitis, reporting earlier recovery, stronger regain of body weight, reduced inflammatory infiltrates and lower colonic myeloperoxidase activity; in MC1R-deficient mice, KPV rescued all treated animals from DSS-induced death [5]. Xiao and colleagues later loaded KPV into hyaluronic-acid-functionalised nanoparticles (about 272 nm) and delivered them orally in a chitosan/alginate hydrogel; the targeted formulation both accelerated mucosal healing and reduced TNF-α in a mouse ulcerative-colitis model, outperforming untargeted KPV nanoparticles [6].

What the compound is examined for

• NF-κB reporter and cytokine-release assays in epithelial and immune cell lines [4].
• PepT1 transport kinetics and competition with other di/tripeptides [4].
• Receptor-independence: activity in MC1R-deficient backgrounds [5].
• Structure–activity relationships around the proline and valine positions [2].
• Colon-targeted formulation and nanoparticle delivery [6].

Practical notes

At 342 g/mol, KPV is closer in size to a small molecule than to most peptides, and the C-terminal valine and N-terminal lysine make it a good substrate for PepT1 and other oligopeptide transporters. It is water-soluble, contains no oxidation-prone residues, and is comparatively stable in solution. Some literature uses the N-acetylated, C-amidated form (Ac-KPV-NH2), which has different stability and transport characteristics from the free tripeptide; this listing supplies the free tripeptide.

What the research does not establish

All in-vivo evidence for KPV comes from mouse colitis models, with no human clinical trial of the tripeptide published in an indexed journal. The PepT1 uptake mechanism has been demonstrated in cell lines and inferred in vivo, but the intracellular target through which KPV blocks NF-κB activation has not been identified. The anti-inflammatory effect has been studied almost exclusively in intestinal inflammation; claims for skin, joint or systemic conditions rest on the α-MSH parent literature rather than on KPV itself. No KPV product is approved by any regulator. This material is supplied for in-vitro laboratory research only.

Format. Lyophilised white powder (acetate salt) in a sealed glass vial with rubber stopper and aluminium crimp cap.

Reconstitution. Add bacteriostatic water or sterile buffer slowly down the side of the vial and swirl gently until dissolved; the tripeptide is freely water-soluble. Use the reconstitution calculator to convert vial content to a working concentration.

Storage. Lyophilised vials: 2–8 °C, protected from light; suitable for longer-term storage at −20 °C. Reconstituted solution: 2–8 °C and use within 14 days; avoid repeated freeze–thaw cycles.

Handling. KPV contains no cysteine, methionine or tryptophan and is comparatively stable, but as a small di/tripeptide-transporter substrate it is readily taken up and degraded by living cells, so timing of exposure in cell assays should be controlled. Wear gloves and eye protection. For in-vitro laboratory research only — not for human or veterinary use.