Overview
GHK-Cu (Glycyl-L-Histidyl-L-Lysine copper complex) is a naturally occurring copper-binding tripeptide first isolated from human plasma in the 1970s. Plasma GHK levels have been documented to decline with age, prompting extensive preclinical research into the compound’s roles in dermal remodeling, angiogenesis, and gene expression regulation (Pickart, 2008 — PMID: 18687533).
History
GHK was first characterized by Loren Pickart in 1973 as a factor in human plasma that influenced hepatic cell culture behavior. Subsequent research identified its high-affinity binding to copper ions and its role in transporting copper across cell membranes. Over decades, research has broadened to investigate its activity in dermal matrix remodeling, hair follicle biology, and modulation of gene expression patterns in preclinical models (Pickart & Margolina, 2018).
Structure & Molecular Data
| CAS Number | 89030-95-5 |
| Molecular Formula | C₁₄H₂₃CuN₆O₄⁺ |
| Molecular Weight | 402.92 g/mol |
| Amino Acid Count / Structure | 3-amino-acid tripeptide with copper ion complex |
| PubChem CID | 16132295 |
| Sequence | Gly-His-Lys (complexed with Cu²⁺) |
| Appearance | Lyophilized blue-to-teal powder (due to copper complex) |
| Storage | Store at -20°C. Protect from light. |
| Solubility | Soluble in sterile water |
Compound Class & Mechanism
GHK-Cu functions as a copper delivery peptide, binding copper ions with high affinity and facilitating their uptake into target cells. In preclinical research, copper delivered by GHK has been associated with activity of copper-dependent enzymes including lysyl oxidase, superoxide dismutase, and cytochrome c oxidase.
Beyond copper transport, research has documented that GHK-Cu modulates a broad spectrum of gene expression, with reported influence on the expression of more than 4,000 human genes in preclinical transcriptomic studies. Research domains affected include extracellular matrix remodeling, antioxidant response, DNA damage repair, and dermal pathway biology (Pickart et al., 2015 — PMID: 26110357).
Research Findings
GHK-Cu has been investigated in preclinical research spanning dermal biology, hair follicle studies, angiogenesis research, and gene expression analysis. Published research has documented findings in the following domains:
Key Research Areas
- Dermal Research: collagen/elastin remodeling, dermal fibroblast activity in preclinical models
- Hair Follicle Research: follicle cycling dynamics in research models
- Angiogenesis: VEGF-associated pathway activity in controlled experimental settings
- Gene Expression: transcriptomic profile analysis in preclinical cell culture models
Collectively, the breadth of research literature surrounding GHK-Cu — spanning dermal biology, hair research, wound healing models, and gene expression — has made it one of the most extensively studied copper-binding tripeptides in biomedical research (Pickart & Margolina, 2018).
Research Context
Researchers study GHK-Cu to investigate the biological roles of copper-binding peptides in tissue remodeling, dermal biology, and gene expression modulation. The compound is uniquely positioned in research as both an endogenously occurring molecule whose plasma concentration declines with age and a widely referenced tool for investigating copper-dependent cellular processes.
References
Pickart L. (2008). The human tri-peptide GHK and tissue remodeling. Journal of Biomaterials Science, Polymer Edition. PMID: 18687533
Pickart L., Vasquez-Soltero JM., Margolina A. (2015). GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. BioMed Research International. PMID: 26110357
Pickart L., Margolina A. (2018). Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. International Journal of Molecular Sciences.
Maquart FX. et al. (1993). Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Letters.
Pickart L. (1982). The biological effects and mechanism of action of the plasma peptide glycyl-L-histidyl-L-lysine. Lymphokines.
Miller DM. et al. (1990). Effect of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation. Advances in Experimental Medicine and Biology.
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