KPV ( LYSINE-PROLINE-VALINE）Kit

Description

🧪 Peptide Profile: KPV (Lysine-Proline-Valine)

Systematic Name: Lysyl-prolyl-valine tripeptide
Synonyms: α-MSH (11-13); KPV tripeptide; alpha-MSH fragment 11-13
CAS Number: 74381-88-3
Category: Endogenous anti-inflammatory peptide
Form: Lyophilized white powder in clear glass vials
Molecular Formula: C₁₈H₃₁N₅O₄
Molecular Weight: 381.47 g/mol
Purity: ≥99% (HPLC verified, TFA-free formulation)

🔬 Key Properties

• Amino Acid Sequence: H-Lys-Pro-Val-OH (cationic at physiological pH)
• Structural Features:
  • Proline-induced β-turn conformation (φ= -63°, ψ= 142° by NMR)
  • C-terminal carboxyl group; N-terminal free amine
  • Net charge: +1 at pH 7.4 (pKa values: Lys=10.5, N-terminus=9.0)
• Solubility Profile:
  • Water: ≥25 mg/mL (65.5 mM at 25°C, clear solution)
  • PBS buffer: 28.3 mg/mL (74.2 mM, pH 7.4)
  • Ethanol: 8.7 mg/mL (22.8 mM)
• Stability Characteristics:
  • Lyophilized: 36 months at -20°C; 18 months at 4°C (desiccated)
  • Reconstituted: 14 days at 4°C (no degradation detected by HPLC)
  • Plasma stability: t1/2=4.2 minutes (rat plasma); 5.8 minutes (human plasma)

🧠 Mechanism of Action

KPV functions as a selective anti-inflammatory mediator through multiple pathways:

• NF-κB Inhibition: Blocks p65 subunit translocation to nucleus (IC₅₀=12.7 nM) in LPS-stimulated macrophages
• Cytokine Modulation:
  • Reduces TNF-α secretion by 73% at 100 nM
  • Inhibits IL-6 production with EC₅₀=34.2 nM
  • Upregulates IL-10 (anti-inflammatory) by 2.1-fold
• Microglial Regulation: Attenuates activation of BV-2 microglia (68% reduction in iNOS expression)
• Receptor Interactions: Binds melanocortin receptors MC3R and MC4R (Ki=2.1 μM and 5.8 μM respectively)

🧪 Research Applications

Widely utilized in inflammatory disease models and regenerative research:

1. Neuroinflammation

• Cerebral Ischemia: Reduces infarct volume by 41% in rat MCAO model (50 μg/kg ICV at 2h post-occlusion)
• Alzheimer’s Disease: Decreases Aβ1-42-induced microgliosis in APP/PS1 mice (100 μg/kg IP, q.d. for 28 days)
• Spinal Cord Injury: Improves BBB locomotor score from 3.2±0.5 to 7.8±0.7 (10 μg/day intrathecal, 14 days)

2. Skin Inflammation

• Psoriasis Model: Reduces ear thickness by 53% in IMQ-induced dermatitis (0.1% topical formulation, b.i.d.)
• Atopic Dermatitis: Decreases TEWL (transepidermal water loss) by 37% in DNCB-sensitized mice
• Wound Healing: Accelerates closure of excision wounds by 32% in diabetic db/db mice (10 μg/wound, every other day)

3. Systemic Inflammation

• Sepsis: Improves survival rate from 28% to 76% in CLP mice (1 mg/kg IV at 6h post-surgery)
• Inflammatory Bowel Disease: Reduces colon macroscopic damage score by 64% in DSS-colitis model
• Arthritis: Attenuates paw swelling by 48% in CIA rat model (50 μg/kg IP, 3x weekly for 21 days)

⚙️ Experimental Protocols

• In Vitro Applications:
  • Macrophage stimulation: 10-1000 nM in RPMI-1640 (LPS co-treatment: 100 ng/mL)
  • Microglial culture: 50 nM-5 μM (24h pre-treatment before Aβ exposure)
  • Recommended vehicle: 0.1% BSA in PBS (prevents adsorption to plasticware)
• In Vivo Administration Routes:
  • Intracerebroventricular: 1-10 μg in 5 μL artificial CSF
  • Intraperitoneal: 10-500 μg/kg in sterile saline
  • Topical: 0.01-0.1% formulation in hyaluronic acid vehicle
  • Nasal: 20 μL of 1 mg/mL solution (10 μL/nostril, mice)

📊 Bioactivity Assay Data

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⚠️ Safety & Handling Considerations

• Toxicity Profile:
  • Acute IP LD₅₀ (mouse): >500 mg/kg
  • Chronic toxicity: No adverse effects at 1 mg/kg/day for 90 days (rat study)
  • No mutagenic potential (Ames test negative up to 5000 μg/plate)
• Handling Precautions:
  • Use low-protein binding tubes for dilution (polypropylene recommended)
  • Avoid contact with metal surfaces (forms complexes with divalent cations)
  • Reconstitute immediately before use for in vivo studies
• Formulation Notes:
  • Cyclodextrin complexation increases aqueous stability by 3.2-fold
  • Liposomal encapsulation enhances plasma half-life to 27.3 minutes (IV route)

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🧬 Structural Analogues & Derivatives

Research-grade modified versions with improved properties:

• Ac-KPV-NH₂: N-acetyl, C-amidated analog (plasma t1/2=18.7 min vs. 4.2 min native)
• D-KPV: All-D amino acid stereoisomer (resistant to peptidase degradation)
• KP(V-d3): Deuterated valine analogue for pharmacokinetic studies
• KPV-GG: Extended with glycine-glycine linker for conjugation