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What Is KPV?

KPV (Lys-Pro-Val; CAS 67727-97-3) is a synthetic tripeptide corresponding to residues 11–13 of α-melanocyte-stimulating hormone (α-MSH), with the sequence H-Lys-Pro-Val-NH₂. The compound is derived by isolating the C-terminal tripeptide sequence of the endogenous melanocortin peptide and retaining its amidated C-terminus. KPV has a molecular weight of approximately 341.4 g/mol and molecular formula C₁₆H₃₁N₅O₃, and is registered in PubChem under CID 161360. Despite its minimal three-residue structure, KPV retains measurable biological activity at MC1R and has been studied for anti-inflammatory pharmacology in research contexts, including applications in mucosal inflammation models where its small molecular size facilitates tissue penetration and epithelial uptake.

Chemical Properties

Property	Value
Common Name	KPV; Lys-Pro-Val
CAS Number	67727-97-3
Molecular Formula	C₁₆H₃₁N₅O₃
Molecular Weight	~341.4 g/mol
Peptide Length	3 amino acids (tripeptide)
Sequence	H-Lys-Pro-Val-NH₂
Origin Sequence	Residues 11–13 of α-MSH
Primary Receptor Activity	MC1R (partial agonist); anti-inflammatory pathway activity
PubChem CID	161360
Peptide Class	Melanocortin-derived tripeptide; α-MSH C-terminal fragment

Historical Development and Discovery

KPV was identified in the course of systematic structure-activity studies on α-MSH during the 1970s and 1980s, when researchers were mapping which regions of the 13-residue α-MSH sequence were responsible for its well-documented anti-inflammatory and immunomodulatory effects. The N-terminal acetylated sequence (Ac-SYSMEH) and the core pharmacophore (HFRW) were known to be critical for melanocortin receptor binding and eumelanin induction. By contrast, the C-terminal tripeptide Lys-Pro-Val (KPV, positions 11–13) was found to retain anti-inflammatory activity independently of the full-length peptide’s receptor-binding pharmacophore, suggesting that KPV could engage molecular targets distinct from—or partially overlapping with—the classic HFRW-dependent MC1R agonism pathway.

Subsequent research demonstrated that KPV retains the amidated C-terminal group characteristic of native α-MSH (Val-NH₂), and that this terminal modification contributes to its biological activity and protease resistance. The tripeptide became of particular research interest in the context of mucosal inflammation because of its compact size: at only three residues, KPV is small enough to traverse epithelial barriers and has been explored in research models using nanoparticle and hydrogel delivery platforms designed to concentrate the compound at mucosal surfaces. As a component of the KLOW research stack—which combines BPC-157, GHK-Cu, Ac-SDKP, and KPV—the compound is studied alongside complementary peptides addressing tissue repair and anti-inflammatory pathways through distinct molecular mechanisms.

Chemical Architecture and Structural Features

KPV is among the smallest peptide research compounds in the melanocortin-derived class. Its three-residue structure provides minimal steric complexity while retaining the proline residue that imposes a fixed pyrrolidine ring constraint on the central backbone, forcing a distinctive cis or trans isomer distribution at the Lys-Pro peptide bond that influences the compound’s three-dimensional shape in solution.

Structural Feature	Detail
N-terminus	Free amine (H-Lys¹); epsilon-amino group on lysine side chain also free
C-terminus	Amidated (Val³-NH₂); matches native α-MSH C-terminal modification
Residue 1 (Lys)	Lysine; side chain ε-NH₂ provides positive charge at physiological pH; participates in ionic interactions
Residue 2 (Pro)	Proline; pyrrolidine ring nitrogen creates restricted backbone; no NH hydrogen donor at Pro; Lys-Pro bond prone to cis/trans isomerism
Residue 3 (Val)	Valine; branched aliphatic side chain; C-terminally amidated
Source sequence	Positions 11–13 of α-MSH (Lys¹¹-Pro¹²-Val¹³-NH₂)
Key structural difference from parent α-MSH	Lacks N-terminal Ac-Ser-Tyr-Ser-Nle-Glu and central His-D-Phe-Arg-Trp pharmacophore

The proline at position 2 of KPV is pharmacologically significant: the pyrrolidine ring of proline prevents the formation of a conventional secondary amide NH hydrogen bond at that peptide linkage, and the cyclic backbone geometry enforces a constrained turn conformation in the tripeptide chain. This conformational preference distinguishes KPV from tripeptides lacking proline and may contribute to its interaction geometry at cellular targets. The two positive charges carried by KPV at physiological pH—from the alpha-amino group of Lys and the epsilon-amino group of its side chain—facilitate electrostatic interactions with anionic components of cell membranes and extracellular matrix, potentially contributing to cellular uptake and mucosal retention properties observed in research delivery studies.

Research Mechanisms

• MC1R partial agonism: KPV retains a portion of α-MSH’s MC1R-binding activity, acting as a partial agonist with lower efficacy than the full-length α-MSH or its potent analogues. MC1R partial agonism contributes to cAMP elevation and downstream anti-inflammatory signaling without the full melanogenic drive of higher-affinity melanocortin peptides.
• NF-κB pathway inhibition: Research has shown KPV can inhibit nuclear factor kappa-B (NF-κB) activation, reducing transcription of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. This anti-inflammatory mechanism may operate partly independently of MC1R through direct interaction with intracellular signaling components.
• Epithelial barrier research applications: KPV’s small molecular size (3 residues, ~341 Da) allows research evaluation of delivery through mucosal epithelial layers, making it suitable for nanoparticle-based delivery research targeting intestinal mucosa in inflammation models.
• Melanocortin anti-inflammatory pathway engagement: As a fragment of α-MSH, KPV engages the broader melanocortin anti-inflammatory network, which suppresses mast cell activation, reduces leukocyte recruitment, and modulates macrophage polarization toward anti-inflammatory phenotypes in research model systems.

Research Areas

What does KPV research reveal about mucosal inflammation?

KPV has been a subject of research in models of mucosal and intestinal inflammation due to its compact size and ability to penetrate epithelial surfaces when delivered via nanoparticle or hydrogel formulations. Research programs have used colitis models to assess whether targeted mucosal delivery of KPV reduces inflammatory markers, alters cytokine profiles, and modifies tissue histology in intestinal tissue. The tripeptide’s NF-κB-inhibitory activity has been proposed as the mechanism underlying reductions in TNF-α, IL-1β, and IL-6 observed in such research models. These studies use KPV as a proof-of-concept tool for investigating whether α-MSH-derived fragments retain anti-inflammatory biological activity at mucosal surfaces accessible to topical or oral nanoparticle delivery approaches.

How is KPV used in melanocortin receptor pharmacology research?

As the C-terminal tripeptide fragment of α-MSH, KPV has been used in receptor pharmacology research to define which regions of the α-MSH sequence are necessary versus sufficient for biological activity. Competitive binding assays using KPV against full-length α-MSH and high-affinity analogues such as Melanotan I and Melanotan II have helped quantify the contribution of the C-terminal tripeptide to MC1R binding affinity. These structure-activity relationship studies have demonstrated that the HFRW core pharmacophore is the primary determinant of high-affinity MC1R binding, while the C-terminal KPV region contributes secondary interactions that modulate receptor engagement and may influence receptor conformation or signal transduction efficiency.

What research explores KPV and skin barrier or dermal research?

Research evaluating KPV in skin-related contexts has examined whether the compound influences keratinocyte cytokine production, mast cell degranulation, and dermal inflammatory mediator profiles. MC1R is expressed on keratinocytes and dermal immune cells, and α-MSH-derived peptides have been studied for potential roles in skin barrier function and UV-induced inflammation modulation. KPV, as the C-terminal fragment retaining partial MC1R activity, has been used alongside intact α-MSH in comparative research designs to dissect which pharmacological activities segregate to the N-terminal receptor-binding pharmacophore versus the C-terminal KPV fragment. These designs provide information on the structural requirements for MC1R-mediated skin immune modulation in research models.

Frequently Asked Questions

What is KPV?

KPV (Lys-Pro-Val; CAS 67727-97-3) is a synthetic tripeptide corresponding to the C-terminal three amino acids (positions 11–13) of α-melanocyte-stimulating hormone (α-MSH). Its sequence is H-Lys-Pro-Val-NH₂, retaining the amidated C-terminus of the parent α-MSH peptide. KPV is studied in research contexts for partial MC1R agonist activity and anti-inflammatory pharmacology, particularly in models of mucosal and skin-related inflammation. It has a molecular weight of approximately 341.4 g/mol.

What is KPV derived from?

KPV corresponds to positions 11–13 of α-melanocyte-stimulating hormone (α-MSH), the endogenous 13-amino acid peptide derived from proopiomelanocortin (POMC) processing. In the full α-MSH sequence (Ac-Ser-Tyr-Ser-Nle-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂), the C-terminal KPV tripeptide follows the HFRW pharmacophore core and the Gly¹⁰ linker. Research has established that the KPV tripeptide retains biological activity independently of the intact α-MSH sequence, making it a useful minimal fragment for mechanistic pharmacology studies.

What receptor does KPV target?

KPV exhibits partial agonist activity at MC1R (melanocortin 1 receptor), the primary target of its parent peptide α-MSH. Its receptor binding affinity is substantially lower than intact α-MSH or high-affinity analogues such as Melanotan I or Melanotan II, which contain the complete HFRW pharmacophore core required for high-affinity melanocortin receptor binding. Research also indicates that KPV’s anti-inflammatory effects may involve pathways partially independent of MC1R, including direct NF-κB pathway inhibition in immune cells, which may account for biological activities observed at concentrations above receptor-binding saturation thresholds.

What is the molecular formula and weight of KPV?

KPV (H-Lys-Pro-Val-NH₂) has a molecular formula of C₁₆H₃₁N₅O₃ and a molecular weight of approximately 341.4 g/mol. CAS registry number 67727-97-3 uniquely identifies this compound. PubChem registers KPV under CID 161360. The tripeptide structure comprises lysine (Lys, K), proline (Pro, P), and valine (Val, V) residues with a free N-terminal amine on lysine, a free epsilon-amino group on the lysine side chain, and an amidated C-terminal valine.

How does KPV relate to the KLOW stack?

KPV is one of four research compounds comprising the KLOW stack formulation, alongside BPC-157 (CAS 137525-51-0), GHK-Cu (CAS 89030-95-5), and Ac-SDKP (CAS 64338-12-5). Each component addresses distinct aspects of tissue repair and inflammatory signaling: BPC-157 supports angiogenesis and growth factor receptor upregulation, Ac-SDKP contributes anti-fibrotic and anti-inflammatory signaling, GHK-Cu stimulates collagen synthesis and antioxidant defense, and KPV contributes melanocortin-derived anti-inflammatory signaling through MC1R partial agonism and NF-κB pathway modulation. The KLOW formulation is used in research settings to evaluate whether combinations of mechanistically distinct tissue-active peptides produce additive or synergistic outcomes in research models.

What role does proline play in KPV’s structure?

Proline at the central position of KPV (residue 2) imposes a fixed pyrrolidine ring constraint on the peptide backbone. Unlike standard amino acids, proline’s nitrogen is part of a cyclic structure, eliminating the NH hydrogen bond donor at that position and restricting the backbone phi angle to a narrow range. This forces the Lys-Pro peptide bond into a distribution of cis and trans conformational isomers and introduces a structural bend in the tripeptide chain. The proline-induced conformation influences how KPV interacts with cellular targets and may contribute to its resistance to certain aminopeptidases that have reduced activity at Pro-containing sequences.

What makes KPV useful in mucosal delivery research?

KPV’s small molecular size (~341 Da, 3 residues) gives it favorable properties for research into mucosal delivery. Larger peptides face significant barriers to traversing intestinal epithelium and mucus layers, whereas tripeptides of KPV’s size can be transported via peptide transporter systems (particularly PepT1, the intestinal oligopeptide transporter) expressed on enterocytes. Research programs using nanoparticle encapsulation—including chitosan, PLGA, and nanoclay-based platforms—have used KPV as a model anti-inflammatory tripeptide to evaluate whether targeted colonic delivery can concentrate the compound at inflamed mucosal surfaces and achieve local anti-inflammatory effects while minimizing systemic exposure.

Is KPV the same as the alpha-MSH C-terminal fragment used in older melanocortin research?

Yes. KPV corresponds directly to the C-terminal tripeptide fragment of α-MSH (positions 11–13: Lys¹¹-Pro¹²-Val¹³-NH₂) and is the same sequence investigated in early melanocortin structure-activity research from the 1980s and 1990s that sought to map biological activity to specific regions of the α-MSH backbone. Early work established that the N-terminal fragment (α-MSH 1–10) retained core receptor binding activity, while the C-terminal fragment (KPV, α-MSH 11–13) contributed residual anti-inflammatory and modulatory activity. This historical research laid the pharmacological foundation for modern interest in KPV as an isolated research compound.

Published Research

The following peer-reviewed publications have examined KPV and related C-terminal α-MSH fragments in research contexts. These citations are provided for scientific reference and do not constitute endorsement of any specific application of the compound outside registered research programs.

• Cannon JG, Tatro JB, Reichlin S, Dinarello CA. Alpha melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1. J Immunol. 1986;137(6):2232–2236. PMID 3018075
• Bhardwaj RS, Schwarz A, Becher E, et al. Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes. J Immunol. 1996;156(7):2517–2521. PMID 8786315
• Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. 2004;56(1):1–29. PMID 15001661
• Laroui H, Viennois E, Xiao B, et al. Fab’-bearing siRNA TNFalpha-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis. J Control Release. 2014;186:41–53. PMID 24814062
• Luger TA, Brzoska T. alpha-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs. Ann Rheum Dis. 2007;66 Suppl 3:iii52–55. PMID 17934082
• Getting SJ. Targeting melanocortin receptors as potential novel anti-inflammatory therapies. Pharmacol Ther. 2006;111(1):1–15. PMID 16289331

Research Use Only Disclaimer

KPV (Lys-Pro-Val; CAS 67727-97-3) is intended for laboratory research purposes by qualified professionals only. Not for human, animal, diagnostic, or therapeutic use. This compound has not been evaluated by the FDA for clinical application, is not manufactured to pharmaceutical standards, and all applicable local, state, and federal regulations governing research compounds apply.