Overview
GHK-Cu is the copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine (GHK), also catalogued as prezatide copper or copper tripeptide-1. GHK was first described in 1973 as a tripeptide in human serum that prolonged the survival of normal liver cells in culture1, and it has an affinity for copper(II) ions2.
Subsequent research has focused on connective tissue: collagen and glycosaminoglycan synthesis in fibroblast cultures, extracellular matrix accumulation and remodelling in rat wound chamber models, and, more recently, gene expression analyses2,3,7. The presence of a GHK triplet in the alpha 2(I) chain of type I collagen has been noted as a possible source of the tripeptide at sites of tissue injury2.
Mechanism of action
As described in the research literature
As described in the research literature, GHK-Cu stimulated collagen synthesis in fibroblast cultures independently of any change in cell number2. In a rat wound chamber model, GHK-Cu was associated with graded increases in dry weight, DNA, total protein, collagen and glycosaminoglycan content, and with increased type I and type III collagen mRNA but not TGF-beta mRNA; a control tripeptide had no significant effect3.
The same model has been used to examine matrix turnover. GHK-Cu was reported to modulate the expression and activation of matrix metalloproteinases MMP-2 and MMP-9 during later stages of healing4, and to increase decorin mRNA while decreasing biglycan mRNA, with decorin stimulation also observed in dermal fibroblast cultures5.
Reviews by Pickart and colleagues propose that GHK functions as a copper complex and summarise gene expression data suggesting that it regulates multiple biochemical pathways; these reviews are authored by the peptide's original discoverer and should be read alongside the primary studies6,7.
Research areas
What published studies have examined
Collagen synthesis in fibroblast culture
In vitro work examined collagen production by fibroblasts exposed to GHK-Cu across a concentration range, measured independently of cell number2. Decorin expression in rat dermal fibroblast cultures was examined in later work5.
Sources [2] [5]
Extracellular matrix in wound chamber models
Rat wound chamber studies examined dry weight, total protein, collagen, elastin and glycosaminoglycan content, along with collagen and TGF-beta mRNA3. Follow-up studies in the same model characterised glycosaminoglycan composition and the small proteoglycans decorin and biglycan5.
Sources [3] [5]
Matrix metalloproteinase regulation
Wound fluid and wound tissue from rat chambers were analysed for interstitial collagenase, MMP-2 and MMP-9 activity over the course of healing, comparing GHK-Cu with saline controls4. The study examined how these enzymes are selectively expressed or activated at different stages of remodelling4.
Sources [4]
Gene expression analyses
Reviews have collated data from gene expression studies suggesting that GHK modulates many genes linked to tissue repair, inflammation and protection pathways7. A separate review covers its proposed role in skin regeneration pathways, including modulation of metalloproteinases and their inhibitors6.
Sources [6] [7]
Specifications
- Sequence
- Gly-His-Lys (GHK), as a copper(II) complex
- Molecular formula
- C14H22CuN6O4
- Molecular weight
- 401.9 g/mol
- CAS number
- 89030-95-5 (copper complex; 49557-75-7 is the copper-free GHK peptide)
Vial
- Form
- Blue to blue-violet lyophilised powder in a sealed vial (50 mg or 100 mg)
- Storage
- Store lyophilised powder at -20 °C, protected from light and moisture. Once reconstituted, keep refrigerated at 2 to 8 °C and protect from light.
- Solubility and reconstitution
- Reconstitute with bacteriostatic water. Add the diluent slowly down the inside wall of the vial and swirl gently until clear; do not shake.
Units
- Form
- Measured units with a stated amount per unit, 30 or 60 to a resealable foil pouch
- Storage
- Store in a cool, dry place in the sealed pouch, away from direct light.
- Solubility and reconstitution
- Supplied ready to use: each unit is pre-measured, so no reconstitution is required.