KPV

KPV (Lys-Pro-Val) is the C-terminal tripeptide of alpha-melanocyte stimulating hormone (alpha-MSH), corresponding to positions 11-13 of the 13 amino acid neuropeptide. Despite representing only the terminal three residues — outside the canonical His-Phe-Arg-Trp pharmacophore (positions 6-9) that drives high-affinity melanocortin receptor binding — KPV retains measurable anti-inflammatory biological activity in published research models, making it an important minimal pharmacophore reference for melanocortin system research.

Alpha-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) is the 13 amino acid POMC-derived neuropeptide that activates all five melanocortin receptors (MC1R-MC5R). The receptor-binding pharmacophore is the His-Phe-Arg-Trp tetrapeptide at positions 6-9 — this core sequence is essential for productive MCR binding and is absent from KPV. The biological activity of KPV therefore either reflects very low-affinity partial MCR agonism (requiring much higher concentrations than full-length alpha-MSH for equivalent MCR occupancy) or receptor-independent mechanisms such as direct intracellular interactions with NFkB or MAPK pathway components.

The anti-inflammatory research profile of KPV has been characterised in immune cell models and intestinal epithelial systems. Brzoska et al. (Endocrine Reviews, 2008) provided comprehensive comparative data on alpha-MSH and related peptides including KPV in immune cell preparations, establishing that KPV produces IL-6, TNF-alpha, and IL-12 suppression at nanomolar to low micromolar concentrations — substantially higher than alpha-MSH's picomolar to nanomolar effective range, consistent with weak MCR interaction. The anti-inflammatory signalling has been attributed to NFkB pathway suppression, reducing inflammatory cytokine gene transcription.

Intestinal epithelial biology is the most active current research area for KPV. MC1R, MC3R, and MC5R are expressed on intestinal epithelial cells (Caco-2 cells, primary colonoids), where melanocortin signalling through Gs/cAMP/PKA can modulate NFkB activity and inflammatory gene expression. Published research has used KPV in inflammatory bowel disease research models — examining effects on: transepithelial electrical resistance (TEER) as a measure of epithelial barrier integrity following inflammatory challenge; apical and basolateral IL-6, IL-8, and TNF-alpha secretion; NFkB-luciferase reporter activation in epithelial cells; and tight junction protein expression (occludin, claudin-1, ZO-1) by immunofluorescence.

KPV's tripeptide size (MW 329 Da) provides practical research advantages: excellent aqueous solubility across the pH range (all three residues have high water affinity), rapid cellular uptake, and simple synthesis enabling isotopically labelled variants (deuterated or 13C-labelled) for mechanistic studies. Its minimal size also reduces the likelihood of immune recognition — KPV has no known immunogenic properties in published research.

Structure-activity relationship research compares KPV with alpha-MSH (positions 1-13), NDP-MSH (a potent synthetic analogue), and melanocortin receptor subtype-selective synthetic compounds to establish whether KPV's biological effects are receptor-mediated and which receptor subtypes contribute. Using selective MCR antagonists (HS-024 for MC4R, SHU9119 for MC3R/MC4R) as pre-treatments before KPV in inflammatory assays allows mechanistic attribution.

MW: 329.40 g/mol. CAS: 63631-37-8. Molecular formula: C15H28N4O4. Freely water-soluble. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.

For intestinal epithelial barrier research: Caco-2 cells grown to confluency on Transwell inserts provide the standard intestinal epithelial model for KPV research. Inflammatory challenge with IL-1beta (10ng/mL, apical), TNF-alpha (10ng/mL, apical), or LPS (1ug/mL) for 24 hours before or alongside KPV treatment (1nM-10uM) allows measurement of: TEER by EVOM2 voltohmmeter; apical and basolateral IL-6, IL-8, TNF-alpha by ELISA; and tight junction protein expression by Western blot (occludin, claudin-1, ZO-1). MCR antagonist controls: use SHU9119 (MC3R/MC4R antagonist) and agouti protein (MC1R antagonist) to probe receptor contributions. MW: 329.40 g/mol. Freely water-soluble. Store lyophilised at -20°C. For laboratory and analytical research purposes only.