KPV 10mg

KPV Peptide — Introduction and Research Disclaimer

KPV (Lys-Pro-Val) is a synthetic tripeptide corresponding to the C-terminal fragment of alpha-melanocyte-stimulating hormone (α-MSH). It has garnered significant attention in biomedical research for its potent anti-inflammatory and immunomodulatory properties. KPV is classified as a melanocortin-related peptide that exerts its biological effects primarily through melanocortin receptor subtypes expressed on immune cells and other tissues.

IMPORTANT RESEARCH DISCLAIMER: All products offered by BioSim Peptides, including KPV 10mg, are sold strictly for in vitro laboratory research and experimental purposes only. These products are not intended for human or veterinary use, not for diagnostic or therapeutic purposes, and are not to be used as drugs, food additives, dietary supplements, or cosmetics. Researchers must handle these materials in accordance with all applicable institutional, local, state, and federal regulations. Appropriate personal protective equipment (PPE), biosafety protocols, and institutional review board (IRB) approval (where applicable) must be employed.

Molecular Overview

KPV is a short tripeptide composed of three amino acids in sequence: L-Lysine — L-Proline — L-Valine (single-letter code: K-P-V). The peptide features a molecular formula of C₁₆H₃₀N₄O₄ and a molecular weight of approximately 342.4 g/mol (free base). The CAS registry number assigned to KPV is 67727-97-3.

KPV represents the C-terminal tripeptide (amino acid residues 11–13) of the endogenous neuropeptide α-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂). The biological significance of this C-terminal region was first recognized when researchers observed that truncated fragments of α-MSH retained substantial anti-inflammatory activity despite lacking the N-terminal melanotropic core sequence His-Phe-Arg-Trp that is classically required for melanocortin receptor binding and pigmentary effects.

Key molecular characteristics:

• Sequence: H-Lys-Pro-Val-OH (free acid form)
• Molecular Formula: C₁₆H₃₀N₄O₄
• Molecular Weight: ~342.4 g/mol (free base); counterion-dependent for salt forms
• CAS Number: 67727-97-3
• Solubility: Highly soluble in water (>10 mg/mL) and aqueous buffers
• Isoelectric Point: ~9.5 (basic peptide due to lysine residue)
• Stability: Stable as lyophilized powder at -20°C; susceptible to proteolytic degradation in solution
• Peptide Purity: ≥95% (typical research-grade specification, verified by HPLC and mass spectrometry)

The presence of the N-terminal lysine imparts a positive charge at physiological pH, while the central proline residue introduces conformational rigidity that influences receptor binding geometry and metabolic stability. The C-terminal valine contributes hydrophobic character important for membrane interactions.

Mechanism of Action

KPV exerts its biological effects through multiple intersecting signaling pathways, primarily mediated by interactions with melanocortin receptor (MCR) subtypes expressed on immune and inflammatory cells. The peptide’s mechanism has been extensively characterized in preclinical models of acute and chronic inflammation.

Melanocortin Receptor Engagement

KPV interacts with melanocortin receptors, particularly MC₁R and MC₃R subtypes, which are abundantly expressed on macrophages, monocytes, neutrophils, dendritic cells, and glial cells. Unlike the full-length α-MSH peptide, KPV does not require the canonical His-Phe-Arg-Trp melanotropic sequence for its anti-inflammatory activity, indicating that the C-terminal tripeptide engages melanocortin receptors through a distinct binding mode or activates alternative signaling conformations. Studies utilizing MC₁R and MC₃R knockout models have demonstrated partial but not complete redundancy, suggesting that KPV may signal through both receptor-dependent and receptor-independent mechanisms.

NF-κB Pathway Inhibition

A central mechanism of KPV-mediated anti-inflammatory action involves inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. KPV suppresses IκB kinase (IKK) activation, thereby preventing phosphorylation and subsequent degradation of IκBα, the endogenous inhibitor of NF-κB. Stabilization of the IκBα-NF-κB complex in the cytoplasm prevents nuclear translocation of NF-κB subunits (p50/p65), resulting in attenuated transcription of pro-inflammatory cytokine genes including TNF-α, IL-1β, IL-6, and IL-8.

cAMP-Dependent Signaling

Engagement of melanocortin receptors (which are Gαs-coupled GPCRs) by KPV stimulates adenylate cyclase activity and elevates intracellular cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP activates protein kinase A (PKA), which phosphorylates and inhibits multiple pro-inflammatory signaling intermediates. The cAMP/PKA axis also promotes expression of anti-inflammatory mediators including IL-10 and heme oxygenase-1 (HO-1).

Cytokine Modulation

KPV demonstrates a consistent profile of suppressing pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ) while preserving or enhancing anti-inflammatory mediators (IL-10, IL-1 receptor antagonist). This immunomodulatory balance distinguishes KPV from conventional immunosuppressive agents that broadly suppress immune function.

Additional Mechanisms

Emerging evidence suggests that KPV may also: (a) inhibit p38 MAP kinase and JNK signaling cascades involved in stress-induced inflammation; (b) reduce reactive oxygen species (ROS) production by modulating NADPH oxidase activity in phagocytes; (c) inhibit leukocyte adhesion molecule expression (ICAM-1, VCAM-1) on endothelial cells, thereby reducing inflammatory cell extravasation; and (d) promote resolution of inflammation through enhanced macrophage efferocytosis.

Research Applications

KPV is employed across a diverse range of preclinical research domains investigating inflammatory pathophysiology and potential therapeutic interventions. Below are the principal areas of active investigation:

Inflammatory Bowel Disease Models

KPV has been extensively studied in rodent models of colitis, including dextran sulfate sodium (DSS)-induced and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Research demonstrates that KPV administration reduces colonic mucosal inflammation, decreases myeloperoxidase (MPO) activity, preserves epithelial barrier integrity, and attenuates body weight loss. Colon length, a macroscopic index of colitis severity, is significantly preserved in KPV-treated animals compared to vehicle controls.

Dermatological Inflammation Research

Investigators studying contact hypersensitivity, atopic dermatitis-like lesions, and UV-induced skin inflammation have utilized KPV to examine melanocortin-mediated regulation of cutaneous immune responses. Topical and systemic KPV administration has been shown to reduce dermal inflammatory infiltrates, suppress local cytokine production, and accelerate resolution of experimentally induced skin inflammation.

Ocular Inflammation

Experimental models of uveitis and endotoxin-induced ocular inflammation have been employed to study KPV’s capacity to penetrate ocular barriers and suppress intraocular inflammatory cascades. KPV reduces leukocyte infiltration into the anterior chamber and vitreous cavity and preserves retinal architecture in models of inflammatory eye disease.

Neuroinflammation and CNS Research

KPV has been investigated in models of neuroinflammation, including experimental autoimmune encephalomyelitis (EAE), cerebral ischemia-reperfusion injury, and lipopolysaccharide (LPS)-induced glial activation. Research indicates that KPV can cross the blood-brain barrier to a limited extent, directly modulating microglial activation and suppressing astrocytic NF-κB signaling.

Wound Healing and Tissue Repair

The role of KPV in promoting wound closure and tissue regeneration has been explored in cutaneous wound models. KPV appears to accelerate re-epithelialization, enhance collagen deposition, and modulate the transition from inflammatory to proliferative phases of wound repair.

Pulmonary Inflammation

Models of acute lung injury (ALI) and allergic airway inflammation have employed KPV to investigate melanocortin-mediated regulation of pulmonary inflammatory responses, alveolar macrophage activation, and bronchial epithelial cytokine production.

Key Research Studies

The following studies represent seminal contributions to the understanding of KPV biology and pharmacology. PubMed identifiers (PMIDs) are provided for direct access to primary literature.

Foundational Discovery of C-Terminal α-MSH Anti-Inflammatory Activity

Lipton JM, Catania A. Anti-inflammatory actions of the neuroimmunomodulator alpha-MSH. Immunology Today. The authors comprehensively reviewed the emerging evidence that α-MSH and its C-terminal fragments function as endogenous modulators of inflammation, establishing the conceptual framework for subsequent KPV research. [PMID: 2537804]

Identification of the KPV Tripeptide as the Minimal Active Fragment

Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH. FASEB Journal. This landmark study demonstrated that the C-terminal tripeptide Lys-Pro-Val (KPV) retains the full anti-inflammatory potency of α-MSH in models of acute inflammation, identifying KPV as the minimal pharmacophore responsible for the anti-inflammatory actions of α-MSH. [PMID: 1314907]

Melanocortin Receptor Pharmacology of KPV

Getting SJ, et al. Redundancy of a functional melanocortin 1 receptor in the anti-inflammatory actions of melanocortin peptides: studies in the nouse. Journal of Immunology. Using MC₁R-mutant mice, this study demonstrated that KPV retains anti-inflammatory activity even in the absence of functional MC₁R signaling, providing evidence for MC₁R-independent pathways and implicating MC₃R as a key mediator. [PMID: 10344505]

KPV in Experimental Colitis

Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflammatory Bowel Diseases. This investigation characterized the therapeutic efficacy of KPV in chemically induced colitis models, demonstrating significant reductions in histological inflammation scores, pro-inflammatory cytokine levels, and clinical disease indices. The study identified colonic epithelial cells and lamina propria macrophages as key cellular targets of KPV action. [PMID: 18253952]

Mechanistic Elucidation of NF-κB Suppression

Manna SK, Aggarwal BB. Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. Journal of Immunology. While this study focused on full-length α-MSH, it established the mechanistic paradigm of NF-κB pathway inhibition that underlies the anti-inflammatory activity of melanocortin peptides including KPV, demonstrating inhibition of IκBα phosphorylation and degradation. [PMID: 9692893]

KPV Modulation of Dermal Inflammation

Luger TA, et al. The role of alpha-melanocyte-stimulating hormone in cutaneous biology. Journal of Investigative Dermatology Symposium Proceedings. This comprehensive review contextualized the role of melanocortin peptides, including KPV, in regulating cutaneous immune responses, hair follicle cycling, and epidermal homeostasis. [PMID: 9256881]

KPV in Neuroinflammatory Models

Catania A, et al. The melanocortin system in control of inflammation. The Scientific World Journal. This review synthesized evidence for melanocortin-mediated control of neuroinflammation, including the capacity of KPV and related peptides to modulate microglial and astrocytic inflammatory responses in the central nervous system. [PMID: 20339535]

Handling and Reconstitution Guidelines

Proper handling of KPV is essential to maintain peptide integrity and ensure reproducible experimental results. Researchers should adhere to the following guidelines:

Storage of Lyophilized Peptide

• Store unopened vials of lyophilized KPV at -20°C in a frost-free freezer, protected from light and moisture.
• Allow the sealed vial to equilibrate to room temperature before opening to prevent condensation on the lyophilized cake.
• Lyophilized KPV is stable for ≥24 months when stored under recommended conditions.

Reconstitution Protocol

• KPV is freely soluble in sterile water, 0.9% sterile saline, phosphate-buffered saline (PBS, pH 7.4), and other aqueous buffers.
• Typical reconstitution concentrations range from 1–10 mg/mL depending on experimental requirements.
• Add the reconstitution solvent slowly down the vial wall; avoid directing the solvent stream directly onto the lyophilized cake.
• Gently swirl or vortex briefly to ensure complete dissolution. Avoid vigorous agitation, which may cause foaming or peptide aggregation.
• If solubility issues arise, brief sonication (5–10 seconds) in a bath sonicator may be employed.
• For cell culture applications, sterile-filter (0.22 μm) the reconstituted solution before use.

Aliquoting and Storage of Reconstituted Solutions

• Reconstituted KPV solutions should be aliquoted into single-use volumes to avoid repeated freeze-thaw cycles.
• Store aliquots at -20°C for short-term use (≤4 weeks) or at -80°C for long-term storage (≤6 months).
• Avoid storage at 4°C exceeding 72 hours, as aqueous peptide solutions are susceptible to gradual degradation via hydrolysis and microbial contamination.
• Document the date of reconstitution and aliquot identically for traceability.

Important Handling Precautions

• KPV, like most peptides, is hygroscopic. Minimize exposure of the opened vial to ambient humidity.
• Use sterile, pyrogen-free laboratory consumables and solvents to prevent experimental confounds from endotoxin contamination.
• KPV is susceptible to proteolytic degradation. Avoid contact with non-sterile surfaces and use protease-free conditions where applicable.

Safety and Laboratory Precautions

KPV is classified as a research chemical intended exclusively for laboratory use. Researchers must implement appropriate safety measures:

• Personal Protective Equipment (PPE): Laboratory coat, nitrile gloves, and safety glasses should be worn at all times when handling KPV.
• Engineering Controls: Handle KPV powder in a certified chemical fume hood or biological safety cabinet to prevent inhalation of aerosolized particles.
• Spill Management: In case of a spill, wear appropriate PPE, absorb the material with inert absorbent, and dispose of in accordance with institutional chemical waste procedures.
• First Aid: In case of eye contact, flush with copious amounts of water for at least 15 minutes and seek medical evaluation. For skin contact, wash thoroughly with soap and water. If inhaled, move to fresh air immediately.
• Toxicity Profile: Comprehensive toxicological characterization of KPV is not available. As with all research peptides, KPV should be treated as a potentially hazardous substance. Avoid ingestion, inhalation, and dermal or mucosal contact.
• Disposal: Dispose of unused KPV and contaminated materials as chemical laboratory waste in accordance with institutional environmental health and safety policies.

Frequently Asked Questions

1. What is the difference between KPV and full-length α-MSH?

KPV (Lys-Pro-Val) is the C-terminal tripeptide of α-MSH, representing only three of the thirteen amino acid residues of the full-length hormone. While α-MSH binds with high affinity to all melanocortin receptor subtypes (MC₁R through MC₅R) and mediates both pigmentary and anti-inflammatory effects, KPV selectively retains the anti-inflammatory activity of α-MSH without the melanogenic (pigment-inducing) effects. This dissociation of anti-inflammatory from melanotropic activity makes KPV an attractive molecular probe for studying melanocortin-mediated inflammation independently of pigmentation pathways. KPV is approximately 3–10 times less potent than α-MSH on a molar basis in most anti-inflammatory assays but demonstrates comparable maximal efficacy.

2. What is the recommended storage condition for KPV?

Lyophilized KPV should be stored at -20°C in a desiccated, light-protected environment. Under these conditions, the peptide remains stable for a minimum of 24 months. After reconstitution in sterile aqueous solvent, KPV solutions should be aliquoted and stored at -20°C (short-term, up to 4 weeks) or -80°C (long-term, up to 6 months). Repeated freeze-thaw cycles should be avoided as they promote peptide aggregation and degradation. Researchers should consult the Certificate of Analysis provided with each batch for lot-specific purity and storage data.

3. What solvents can be used to reconstitute KPV?

KPV is highly water-soluble and can be reconstituted in sterile deionized water, 0.9% sterile saline, phosphate-buffered saline (PBS, pH 7.4), Hank’s Balanced Salt Solution (HBSS), or cell culture media. The choice of solvent should be dictated by the downstream experimental application. For cell-based assays, sterile-filtered PBS or culture media is recommended. For in vivo research applications, sterile saline or PBS is typically employed. KPV is not recommended for reconstitution in pure organic solvents (DMSO, ethanol) for biological assays, though limited organic solvent may be used to prepare stock solutions if verified for compatibility with the assay system.

4. Has KPV been tested in human clinical trials?

No. KPV has not been evaluated in human clinical trials. All published research on KPV to date has been conducted in preclinical models, including in vitro cell culture systems and in vivo animal models (primarily rodent). As with all products offered by BioSim Peptides, KPV is for research purposes only and is not approved by the FDA, EMA, or any other regulatory agency for human therapeutic or diagnostic use. Researchers interested in clinical translation should consult the extensive preclinical literature and engage with regulatory authorities regarding Investigational New Drug (IND) requirements.

5. What is the biological half-life of KPV?

The in vivo half-life of KPV is relatively short, consistent with its classification as a small linear peptide susceptible to rapid proteolytic degradation by serum and tissue peptidases. Published pharmacokinetic studies in rodent models indicate a plasma half-life of approximately 15–45 minutes following intravenous or intraperitoneal administration. The proline residue at position 2 confers some resistance to aminopeptidase degradation compared to peptides lacking proline, but the absence of N-terminal modifications (e.g., acetylation) or D-amino acid substitutions renders KPV susceptible to exopeptidase cleavage. Researchers investigating sustained KPV exposure in vivo frequently employ osmotic minipumps, repeated bolus dosing regimens, or encapsulation in nanoparticle delivery systems to extend the effective duration of action.

References

1. Lipton JM, Catania A. Anti-inflammatory actions of the neuroimmunomodulator alpha-MSH. Immunol Today. 1989;10(7-8):247-250. PMID: 2537804.
2. Hiltz ME, Lipton JM. Antiinflammatory activity of a COOH-terminal fragment of the neuropeptide alpha-MSH. FASEB J. 1992;6(6):2282-2286. PMID: 1314907.
3. Getting SJ, et al. Redundancy of a functional melanocortin 1 receptor in the anti-inflammatory actions of melanocortin peptides: studies in the mouse. J Immunol. 1999;162(12):7254-7261. PMID: 10344505.
4. Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease. Inflamm Bowel Dis. 2008;14(3):324-331. PMID: 18253952.
5. Manna SK, Aggarwal BB. Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. J Immunol. 1998;161(6):2873-2880. PMID: 9692893.
6. Luger TA, et al. The role of alpha-melanocyte-stimulating hormone in cutaneous biology. J Investig Dermatol Symp Proc. 1997;2(1):87-93. PMID: 9256881.
7. Catania A, et al. The melanocortin system in control of inflammation. ScientificWorldJournal. 2010;10:1840-1853. PMID: 20339535.