GHK-Cu Peptide
GHK-Cu is a naturally occurring complex formed when the tripeptide GHK (glycine, histidine, lysine) binds to a copper ion. The copper component helps stabilize and deliver GHK to cells. Research suggests GHK-Cu may play an important role in supporting tissue restoration, wound repair, and immune response. These ideas stem from its perceived ability to stimulate production of collagen, elastin, and glycosaminoglycans—key elements of the extracellular matrix.
Beyond potential effects on the matrix, GHK-Cu is also studied for antioxidant and anti-inflammatory properties that may help shield cells from free-radical damage.
Chemical Makeup
Molecular Formula: C₁₄H₂₃CuN₆O₄
Molecular Weight: 340.38 g/mol
Other Known Titles: Glycyl-L-histidyl-L-lysine copper complex; Copper tripeptide-1; Prezatide copper acetate; UNII-8L70I52FDX; CHEMBL4297243
GHK-Cu and Collagen Synthesis
Studies suggest that GHK-Cu may stimulate collagen synthesis and support tissue recovery in situ. One proposed explanation is the presence of a GHK triplet in the α2(I) chain of type I collagen. The tripeptide sequence glycine–histidine–lysine can be released during collagen breakdown (e.g., after tissue damage or through normal turnover). This peptide fragment is thought to influence cellular signaling, particularly in fibroblasts—cells essential for generating new collagen, elastin, and glycosaminoglycans that maintain the extracellular matrix.
The interaction between the Gly-His-Lys peptide and fibroblasts is believed to initiate a cascade that promotes collagen production and tissue repair. In a month-long study on photodamaged skin, GHK-Cu was compared with other peptides as well as vitamin C and vitamin A derivatives. Endpoints included dermal procollagen, keratinocyte proliferation and differentiation, and cutaneous inflammation. The peptide improved these measures, with reported increases in skin thickness, elasticity, and hydration.
Additional work examined GHK-Cu with hyaluronic acid (HA) and its collaborative effects on collagen synthesis in dermal fibroblasts and an ex vivo skin model. HA of different molecular weights (LMW and HMW) shows distinct biological actions. Experiments exposed fibroblasts to combinations of GHK-Cu and HA and measured collagen I, IV, and VII. Certain mixtures—such as a GHK-Cu:LMW HA ratio of 1:9—produced larger increases in collagen IV than either component alone. Proposed mechanisms include antioxidant activity, support of extracellular matrix components, and modulation of matrix metalloproteinases. Ex vivo testing likewise showed higher collagen IV at the dermal–epidermal junction with optimized GHK-Cu and LMW HA, confirmed by immunofluorescence imaging.
GHK-Cu and Wound Infection
Both animal and clinical studies have proposed that GHK-Cu may reduce inflammation and lower infection risk in wound models, including ischemic wounds. In one murine study, on days 5, 6, 10, and 13, tripeptide–copper–treated wounds contained significantly lower concentrations of TNF-α as well as MMP-2 and MMP-9 than controls, suggesting less inflammatory signaling and reduced extracellular-matrix breakdown in low-perfusion settings.
A clinical trial that added GHK-Cu to standard care for diabetic neuropathic ulcers reported an infection rate of 7% in the GHK-Cu group compared with 34% in the control group.
GHK-Cu and Wound Healing
Studies in rabbits report that GHK-Cu has been tested for its potential in wound healing and under different laser intensities. Animals were observed daily, with weekly biopsies over four weeks to assess inflammation and neovascularization. Compared with controls, the peptide groups showed a shorter time to the first observable granulation tissue and a faster filling of open wounds, along with heightened activity of antioxidant enzymes. These findings suggest a link between early granulation tissue and antioxidant support, with a potential enhancement in vascular development that helps deliver nutrients and oxygen to the injured area.
The previously mentioned rat study on open ischemic wounds also noted a greater reduction in wound area for the GHK-Cu group than for controls on days 3 to 6, 9, and 11 to 13.
In clinical work on diabetic neuropathic ulcers, GHK-Cu combined with standard wound care was reported as more effective than standard care alone, with an apparent three-fold improvement in closure rate. The enhancement of wound closure was more pronounced in larger ulcers (≥100 mm² at entry), reaching a median of 89.2% compared with −10.3% for vehicle (p < 0.01).
Research using standard murine models and skin models adapted to mimic diabetic conditions also evaluated collagen dressings infused with GHK. By the end of week three, wounds treated with the modified dressings nearly reached full closure (99.39%), compared with 69.49% for control dressings without GHK. Analyses indicated higher levels of glutathione and ascorbic acid (key antioxidants), a tentative rise in re-epithelialization, and signals consistent with increased angiogenesis and fibroblast activity—factors involved in collagen synthesis, tissue repair, and regeneration. A potential rise in mast cell activation was also noted, which aligns with early inflammatory phases of wound healing.
GHK-Cu and Active Radicals
Photodamaged skin involves reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive carbonyl species (RCS) that can harm proteins, DNA, and lipids. Studies suggest that the amino-acid sequence in GHK-Cu may act against carbonyl radicals such as 4-hydroxynonenal, acrolein, and malondialdehyde, and may help limit protein glycation.
Additional reports indicate that GHK-Cu may reduce iron release from ferritin—a catalyst of lipid peroxidation—and help limit the formation of iron complexes in damaged tissue and cultured cells. One study described an approximately 87% decrease in iron-catalyzed oxidation under low-temperature conditions.
GHK-Cu has also been observed to reduce ROS production while increasing antioxidant enzyme activity. In an animal model of LPS-induced lung inflammation, the peptide suppressed NF-κB and p38 MAPK signaling, which corresponded with lower levels of pro-inflammatory cytokines such as TNF-α and IL-6.
Further findings suggest that the GHK sequence may exhibit strong antioxidative potential against ROS, including hydroxyl radicals, in some cases outperforming general antioxidant peptides.
GHK-Cu and Wrinkles in Skin Tissue Models
GHK-Cu has been suggested to have potential for improving experimental models of disturbed skin topography, including wrinkles and fine lines. One study posited that GHK-Cu may reduce visible bioindicators while improving skin laxity and clarity. The peptide also reportedly reduced wrinkle depth and increased skin density and thickness after 12 weeks of testing in skin cell models with varying levels of photodamage.
Another investigation compared GHK-Cu with a control compound and with vitamin K. Over 12 weeks, GHK-Cu performed better than controls in reducing epidermal wrinkles and may have increased skin density and thickness.
In a separate 12-week study in mild to advanced photodamage, GHK-Cu appeared to improve laxity, clarity, and firmness. It was also associated with reductions in coarse wrinkles and mottled pigmentation, and histology suggested stimulation of dermal keratinocyte proliferation.
GHK-Cu Peptide is available
for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.
References
- Maquart, F. X., Pickart, L., Laurent, M., Gillery, P., Monboisse, J. C., & Borel, J. P. (1988). Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS letters, 238(2), 343–346. https://doi.org/10.1016/0014-5793(88)80509-x
- Abdulghani, A. A., Sherr, A., Shirin, S., Solodkina, G., Tapia, E. M., Wolf, B., & Gottlieb, A. B. (1998). Effects of creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin-A pilot clinical, histologic, and ultrastructural study. Disease Management and Clinical Outcomes, 4(1), 136-141.
- Jiang F, Wu Y, Liu Z, Hong M, Huang Y. Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex-vivo skin tests. J Cosmet Dermatol. 2023 Sep;22(9):2598-2604. doi: 10.1111/jocd.15763. Epub 2023 Apr 16. PMID: 37062921.
- Canapp, S. O., Jr, Farese, J. P., Schultz, G. S., Gowda, S., Ishak, A. M., Swaim, S. F., Vangilder, J., Lee-Ambrose, L., & Martin, F. G. (2003). The effect of tripeptide-copper complex on healing of ischemic open wounds. Veterinary surgery : VS, 32(6), 515–523. https://doi.org/10.1111/j.1532-950x.2003.00515.x
- Mulder, G. D., Patt, L. M., Sanders, L., Rosenstock, J., Altman, M. I., Hanley, M. E., & Duncan, G. W. (1994). Enhanced healing of ulcers in patients with diabetes by treatment with glycyl-l-histidyl-l-lysine copper. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2(4), 259–269. https://doi.org/10.1046/j.1524-475X.1994.20406.x
- Gul, N. Y., Topal, A., Cangul, I. T., & Yanik, K. (2008). The effects of tripeptide copper complex and helium-neon laser on wound healing in rabbits. Veterinary dermatology, 19(1), 7–14. https://doi.org/10.1111/j.1365-3164.2007.00647.x
- Alven, S., Peter, S., Mbese, Z., & Aderibigbe, B. A. (2022). Polymer-Based Wound Dressing Materials Loaded with Bioactive Agents: Potential Materials for the Treatment of Diabetic Wounds. Polymers, 14(4), 724. https://doi.org/10.3390/polym14040724
- Cebrián, J., Messeguer, A., Facino, R. M., & García Antón, J. M. (2005). New anti-RNS and -RCS products for cosmetic treatment. International journal of cosmetic science, 27(5), 271–278. https://doi.org/10.1111/j.1467-2494.2005.00279.x
- Miller, D. M., DeSilva, D., Pickart, L., & Aust, S. D. (1990). Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation. Advances in experimental medicine and biology, 264, 79–84. https://doi.org/10.1007/978-1-4684-5730-8_11
- Park, J. R., Lee, H., Kim, S. I., & Yang, S. R. (2016). The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget, 7(36), 58405–58417. https://doi.org/10.18632/oncotarget.11168
- Zhang, Q., Yan, L., Lu, J., & Zhou, X. (2022). Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway. Frontiers in molecular biosciences, 9, 925700. https://doi.org/10.3389/fmolb.2022.925700
- Sakuma, S., Ishimura, M., Yuba, Y., Itoh, Y., & Fujimoto, Y. (2018). The peptide glycyl-ʟ-histidyl-ʟ-lysine is an endogenous antioxidant in living organisms, possibly by diminishing hydroxyl and peroxyl radicals. International journal of physiology, pathophysiology and pharmacology, 10(3), 132–138.
- Leyden J., Stephens T., Finkey M., Appa Y., Barkovic S. Skin care benefits of copper peptide containing facial cream. Proceedings of the American Academy of Dermatology Meeting; February 2002; New York, NY, USA.
- Leyden J., Stephens T., Finkey M., Barkovic S. Skin Care Benefits of Copper Peptide Containing Eye Creams. University of Pennsylvania; 2002.
- Finkley M., Appa Y., Bhandarkar S. Copper peptide and skin. In: Elsner P., Maibach H., editors. Cosmeceuticals and Active Cosmetics: Drugs vs. Cosmetics. New York, NY, USA: Marcel Dekker; 2005. pp. 549–563.
Dr. Marinov
Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.