GHK-Cu

GHK-Cu (glycyl-L-histidyl-L-lysine copper(II)) is a naturally occurring copper-binding tripeptide first identified in human plasma by Loren Pickart in 1973. Plasma levels of GHK-Cu decline with age, from approximately 200 ng/mL at age 20 to 80 ng/mL by age 60. It has been the subject of extensive research in dermatology, wound biology, and gene expression studies.

GHK-Cu is a tripeptide with a molecular weight of 403.92 g/mol. The copper(II) ion is chelated by the glycine nitrogen, histidine imidazole nitrogen, and the deprotonated amide nitrogen of the Gly-His bond, forming a highly stable square-planar coordination complex.

This copper-peptide complex has a high affinity constant for Cu²⁺ (log K = 16.44), ensuring stability under physiological conditions while allowing controlled copper release at tissue sites.

• Dermatological research: Studies have examined GHK-Cu's effects on collagen synthesis, glycosaminoglycan production, and dermal fibroblast proliferation in cell culture models (Pickart et al., 2012).
• Gene expression: Connectivity Map analysis identified GHK as modulating expression of 4,000+ human genes, with emphasis on genes associated with tissue remodeling and antioxidant defense (Campbell et al., 2012).
• Wound biology: Preclinical studies have investigated copper peptide effects on wound contraction and re-epithelialization rates.
• Antioxidant research: Studies have examined GHK-Cu's interaction with superoxide dismutase activity and free radical quenching.

GHK-Cu research has identified extensive gene expression and signaling pathway interactions:

• TGF-β/Decorin pathway: GHK-Cu stimulates decorin (a TGF-β regulator) and type I collagen synthesis in dermal fibroblasts. At 10⁻⁹ M, collagen synthesis increased 70% in human skin fibroblast cultures.

• VEGF/FGF-2 angiogenesis: GHK-Cu at nanomolar concentrations upregulated VEGF expression and basic FGF in endothelial cell models, promoting capillary-like tube formation.

• Gene expression (Connectivity Map): Broad Institute analysis identified GHK as modulating 4,000+ human genes. Key pathways affected include:
- DNA repair genes (upregulated)
- Antioxidant response (SOD1, SOD2, SOD3 upregulated)
- Ubiquitin-proteasome system (modulated)
- Stem cell markers (p63 expression modulated)
- Inflammatory mediators (IL-6, TGF-β modulated)

• Copper-dependent enzyme activation: GHK-Cu delivers bioavailable copper to:
- Superoxide dismutase (SOD) — antioxidant defense
- Lysyl oxidase — collagen/elastin cross-linking
- Cytochrome c oxidase — mitochondrial respiration

Active concentration range: 10⁻¹² to 10⁻⁶ M in cell culture (highly potent)

Key preclinical findings with published concentrations:

Pickart et al. (2012, 2015): GHK at 10⁻⁹ M (1 nM) stimulated collagen synthesis by 70% in human dermal fibroblasts. At 10⁻⁶ M, promoted fibroblast and endothelial cell migration in scratch-wound assays.

Campbell et al. (2012): Broad Institute Connectivity Map analysis revealed GHK modulates 4,000+ genes. At 1 µM, GHK reversed gene expression signatures associated with emphysema, metastatic colon cancer, and insulin resistance.

Leyden et al. (2002): Topical GHK-Cu cream (facial application, 8 weeks) improved fine lines by 35.4% and skin density by 34.4% vs vehicle in 71 subjects. Published concentration: not disclosed (cosmetic study).

Canapp et al. (2003): GHK-Cu at 4 µg/cm² accelerated wound contraction in equine wound models.

Typical in vitro concentrations: 1 nM - 10 µM (extremely potent at low nanomolar). GHK-Cu affinity constant: log K = 16.44 for Cu²⁺.

All findings from in vitro, animal, or cosmetic studies. No research-grade clinical trials.

Form: Lyophilized powder, 5mg per vial
Appearance: Blue to blue-violet powder (characteristic of Cu²⁺ complexes)
Molecular Weight: 403.92 g/mol
For In Vitro Research Use Only

Laboratory Preparation:
Add sterile diluent to vial. Gently swirl to dissolve. Solution will have slight blue tint (normal for copper complexes).

Solubility Profile: Freely soluble in water (>50 mg/mL), PBS, DMSO.
Copper Content: 15-17% by mass (ICP-MS verified)

Stability: Lyophilized stable 24 months at -20°C. Solution: 30 days at 2-8°C. Avoid reducing agents (DTT, β-mercaptoethanol). Do not use with chelating agents (EDTA, citrate).

Analytical Testing: HPLC, ESI-MS, LAL endotoxin, sterility, ICP-MS copper content.

This product is for laboratory and in vitro research only. Not for human or animal use.

This content was prepared for informational purposes based on published preclinical research. It does not constitute medical advice or product efficacy claims.

1. 1
   Pickart L, et al. "GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration." Biomed Res Int. 2015;2015:648108. PubMed: 25866797 PubMed
2. 2
   Campbell JD, et al. "A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK." Genome Med. 2012;4(8):67. PubMed: 22937864 PubMed
3. 3
   Pickart L. "The human tri-peptide GHK and tissue remodeling." J Biomater Sci Polym Ed. 2008;19(8):969-88. PubMed: 18644225 PubMed
4. 4
   Leyden J, et al. "Topical application of GHK-Cu results in significant improvement in facial skin." J Cosmet Dermatol. 2002;14:485-99. PubMed
5. 5
   Canapp SO, et al. "The effect of topical tripeptide-copper complex on healing of ischemic open wounds." Vet Surg. 2003;32(6):515-23. PubMed: 14648529 PubMed