GHK-Cu is a naturally occurring copper-binding tripeptide — glycyl-L-histidyl-L-lysine complexed with copper(II) — first isolated from human plasma in 1973 and studied ever since for its effects on fibroblasts, extracellular-matrix turnover and gene expression. This GHK-Cu research peptide guide covers structure, chelation chemistry, published mechanisms, laboratory handling and solution preparation for research scientists working with copper peptides in vitro.
Key takeaways
- GHK is the tripeptide Gly-His-Lys (CAS 49557-75-7, C14H24N6O4, MW 340.38). The 1:1 copper(II) complex GHK-Cu carries CAS 89030-95-5, formula C14H22CuN6O4 and a molecular weight of about 401.9 Da.
- The copper ion is held in a near-square-planar site built from the glycine α-amino nitrogen, the deprotonated glycyl-histidyl amide nitrogen and the histidine imidazole nitrogen — a high-affinity arrangement that is the defining feature of the molecule.
- Loren Pickart isolated GHK from human plasma albumin fractions in 1973; published work reports plasma GHK falling from roughly 200 ng/mL at age 20 to about 80 ng/mL by age 60.
- In fibroblast culture, GHK-Cu has been reported to stimulate collagen synthesis at picomolar-to-nanomolar concentrations (Maquart 1988) and to increase matrix metalloproteinase-2 expression (Siméon 2000).
- A 2012 Genome Medicine analysis reported that GHK partially reversed a gene-expression signature associated with emphysematous lung destruction in cultured fibroblasts — the origin of the “gene modulator” framing used in later reviews.
- Reconstituted GHK-Cu produces a characteristic deep blue solution; loss of that colour suggests the copper complex has dissociated or been displaced.
- GenoPept supplies GHK-Cu as a lyophilised research chemical with a per-batch third-party certificate of analysis. It is for laboratory research use only — not for human or veterinary use.
What is GHK-Cu?
GHK-Cu is a copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine. It is a small, highly water-soluble molecule of about 401.9 Da that occurs naturally in human plasma, saliva and urine, and it is one of the most extensively characterised copper-binding peptides in the biomedical literature. In cosmetic ingredient nomenclature the same entity is listed as copper tripeptide-1.
Two names appear across the literature and need to be kept apart. GHK refers to the free tripeptide with no metal bound; GHK-Cu refers to the 1:1 peptide–copper chelate. They have different formulas, different molecular weights, different CAS numbers and different colours in solution. Papers that describe “GHK” activity in cell culture frequently mean the copper complex forming in situ, because standard culture media contain copper and GHK binds it avidly.
The three residues each do a distinct job. Glycine supplies a free α-amino group and the amide nitrogen of the first peptide bond. Histidine supplies the imidazole ring. Lysine, sitting outside the metal-binding site, gives the molecule a positive charge at physiological pH and is thought to influence how the complex interacts with anionic surfaces such as glycosaminoglycans and cell membranes.
Copper chelation: how GHK holds Cu(II)
The defining property of GHK is high-affinity, selective copper(II) binding. Coordination chemistry studies describe the copper ion being held by the nitrogen of the histidine imidazole side chain, the nitrogen of the glycine α-amino group, and the deprotonated amide nitrogen of the glycine–histidine peptide bond. A weaker axial interaction completes the geometry.
This motif is not accidental. It reproduces the amino-terminal copper- and nickel-binding (ATCUN) arrangement found at the N-terminus of human serum albumin, which begins Asp-Ala-His. Any peptide with histidine in the third position from a free N-terminus can form the same chelate, which is why GHK-Cu is often discussed alongside albumin as part of a plasma copper-shuttling system rather than as a free metal ion carrier.
Practically, three consequences follow for anyone working with the compound in the laboratory:
- Colour is a chemical readout. The d–d electronic transitions of the chelated Cu(II) give the solution a strong blue colour with an absorbance maximum in the visible region. A colourless solution means little or no intact complex.
- Chelators compete. EDTA, citrate, high concentrations of phosphate and strongly coordinating buffers can strip or redistribute the copper. Buffer choice is therefore a real experimental variable, not a detail.
- pH matters. The amide nitrogen must be deprotonated to participate. At markedly acidic pH the complex destabilises; near-neutral to mildly alkaline conditions favour the intact chelate.
Discovery, plasma biology and age decline
GHK was discovered in 1973 by Loren Pickart, who traced a growth-modulating activity in human plasma albumin fractions to a small tripeptide. The original observation was that older liver tissue incubated with plasma from younger donors behaved more like younger tissue; fractionation of that plasma led to Gly-His-Lys.
Published reviews report that circulating GHK declines with age, from approximately 200 ng/mL around age 20 to roughly 80 ng/mL by age 60. That reported decline is the reason the peptide is repeatedly framed in the literature as a candidate endogenous repair signal, and it underpins much of the subsequent cosmetic and wound-model research interest.
A second strand of the origin story concerns where GHK comes from. Sequence analysis places the GHK motif within the alpha-2 chain of type I collagen (the SPARC and collagen-derived fragment hypothesis), which has led investigators to propose that the tripeptide is liberated by proteolysis during tissue injury — a locally generated signal that appears exactly when matrix is being broken down.
What published research reports about GHK-Cu mechanisms
Published work describes GHK-Cu acting on connective-tissue cells at very low concentrations, with effects on both matrix synthesis and matrix remodelling. Investigators have reported stimulation of collagen production in fibroblast culture, changes to metalloproteinase and inhibitor expression, effects on angiogenic signalling, and broad shifts in gene expression. The following summarises what the cited literature reports; none of it is a claim about products supplied by GenoPept.
Matrix synthesis in fibroblast culture
Maquart and colleagues reported in FEBS Letters (1988) that the tripeptide–copper complex stimulated collagen synthesis in cultured fibroblasts, with activity described in the picomolar-to-nanomolar range. Later work from the same group examined the complex in rat experimental wound models and reported increased accumulation of connective-tissue components including collagen, glycosaminoglycans and total protein.
Matrix remodelling: MMPs and TIMPs
Siméon and colleagues reported in Life Sciences (2000) that GHK-Cu stimulated expression of matrix metalloproteinase-2 in fibroblast cultures. Reviews of the field describe GHK-Cu as influencing both the proteolytic arm (MMPs) and the inhibitory arm (TIMP-1 and TIMP-2) of matrix turnover, which is the basis for the “remodelling rather than simply building” description used in the secondary literature.
Gene-expression modulation
The most cited modern result is Campbell and colleagues’ 2012 Genome Medicine paper. Working from lung-tissue transcriptomes, the authors identified a gene-expression signature associated with emphysematous destruction and reported that GHK partially reversed that signature in cultured human fibroblasts, with effects on TGF-β-related and cytoskeletal-remodelling gene sets. Pickart and Margolina’s 2018 review in International Journal of Molecular Sciences collates this and subsequent transcriptomic data.
Wound and repair models
Canapp and colleagues reported in Veterinary Surgery (2003) on topical tripeptide–copper complex in an ischaemic open-wound model, describing accelerated closure relative to vehicle and untreated controls. Parker and colleagues later examined a copper tripeptide complex in an irradiated rat wound model. These are animal models; they describe compound behaviour in a controlled preclinical setting, not outcomes in people.
GHK-Cu specification and physical data
The table below separates the free tripeptide from the copper complex, because catalogue listings, papers and certificates of analysis switch between the two. Molecular weights are the monoisotopic-free average masses reported by PubChem.
| Property | GHK (free tripeptide) | GHK-Cu (copper complex) |
|---|---|---|
| Sequence | Gly-His-Lys | Gly-His-Lys · Cu(II), 1:1 |
| CAS number | 49557-75-7 | 89030-95-5 |
| Molecular formula | C14H24N6O4 | C14H22CuN6O4 |
| Average molecular weight | 340.38 Da | 401.91 Da |
| INCI / cosmetic name | Tripeptide-1 | Copper tripeptide-1 |
| Appearance (lyophilised) | White to off-white powder | Blue to blue-violet powder |
| Solution colour | Colourless | Deep blue |
| Aqueous solubility | Freely soluble | Freely soluble (reported >100 g/L) |
| Copper content by mass | None | ≈15.8% (63.55 / 401.91) |
Solution preparation: concentration reference
The table below is a concentration reference for laboratory solution preparation only. It converts a known mass of lyophilised GHK-Cu in a vial and a chosen diluent volume into a working concentration, so that assay volumes can be calculated. It is not a dosing table and has no application outside a laboratory.
| Mass in vial | Diluent volume | Resulting concentration | Amount in 0.1 mL | Approx. molarity |
|---|---|---|---|---|
| 50 mg | 1 mL | 50 mg/mL | 5,000 mcg | ≈124 mM |
| 50 mg | 2 mL | 25 mg/mL | 2,500 mcg | ≈62 mM |
| 50 mg | 5 mL | 10 mg/mL | 1,000 mcg | ≈25 mM |
| 50 mg | 10 mL | 5 mg/mL | 500 mcg | ≈12 mM |
| 100 mg | 2 mL | 50 mg/mL | 5,000 mcg | ≈124 mM |
| 100 mg | 5 mL | 20 mg/mL | 2,000 mcg | ≈50 mM |
| 100 mg | 10 mL | 10 mg/mL | 1,000 mcg | ≈25 mM |
Molarity is calculated on the 401.91 Da complex. If a certificate of analysis reports the peptide as the free base with a stated net peptide content, adjust the calculation accordingly — see our guide to peptide purity testing for why gross vial mass and net peptide content differ.
Because published cell-culture work operates in the picomolar-to-nanomolar range, laboratory workflows almost always involve serial dilution from a concentrated stock. Preparing a 1 mg/mL intermediate and then diluting stepwise into assay medium is more reproducible than attempting a single large dilution, and it limits how long the concentrated stock is exposed to repeated handling.
- Equilibrate the vial. Bring the lyophilised vial to room temperature before opening to avoid condensation onto the cake.
- Add diluent slowly. Run the diluent down the inner wall of the vial rather than directly onto the powder.
- Dissolve by swirling. Rotate gently until the cake clears. Do not shake or vortex aggressively.
- Confirm the colour. An intact GHK-Cu solution should be visibly blue and free of particulates.
- Aliquot immediately. Split the stock into single-use aliquots so the main stock is never freeze-thawed repeatedly.
- Label fully. Compound, batch number, concentration, diluent, date prepared and operator initials.
Stability, the blue-solution check and handling
Lyophilised GHK-Cu is the stable form and should be kept cold, dry and dark; reconstituted solutions are far less robust and are normally treated as short-lived working material. The single most useful bench check is colour: the blue chelate is its own indicator.
Three degradation routes are worth naming. First, copper displacement: a competing ligand pulls Cu(II) away and leaves free GHK plus a copper–chelator complex. Second, oxidation of the histidine imidazole ring, which is accelerated by light and by free copper acting on dissolved oxygen. Third, ordinary peptide-bond hydrolysis at extremes of pH or temperature, which is slow for a tripeptide but not zero.
For general storage principles that apply across compounds, see our guide on how to store research peptides, and for step-by-step technique see how to reconstitute research peptides.
GHK-Cu versus AHK-Cu and cosmetic peptides
AHK-Cu (copper tripeptide-3, Ala-His-Lys with copper) shares GHK-Cu’s ATCUN-style binding motif but substitutes alanine for glycine at position one. It is studied in a related but narrower literature, with much of the published interest concentrating on hair-follicle and dermal papilla models rather than the broad matrix-remodelling work associated with GHK-Cu.
The wider cosmetic-peptide field divides research compounds into functional classes: carrier peptides such as the copper tripeptides; signal peptides such as palmitoyl pentapeptide-4; and neurotransmitter-inhibitor peptides such as acetyl octapeptide-3. GHK-Cu is unusual in that it is discussed under both the carrier and the signal heading, because it both delivers copper and modulates transcription. Our cosmetic peptides research guide compares the classes directly.
GHK-Cu also appears as a component of multi-peptide research blends. The GLOW and KLOW formulations combine it with BPC-157 and TB-500 (and KPV in KLOW); those combinations are described in our peptide blends guide.
Why concentration ranges look so low
Fibroblast studies report activity at picomolar-to-nanomolar concentrations. A 25 mg/mL stock is roughly 62 mM — around a billion-fold above a 100 pM assay condition, so multi-step serial dilution is unavoidable and dilution error dominates reproducibility.
Why the copper matters analytically
Mass spectrometry of GHK-Cu shows the characteristic copper isotope pattern (63Cu and 65Cu, roughly 69:31). A COA reporting only the 340 Da free-peptide mass has characterised GHK, not the complex.
Quality control: what a GHK-Cu COA should show
A meaningful certificate of analysis for GHK-Cu identifies the compound, quantifies purity and confirms the copper is actually present. Because the copper complex behaves differently from the free peptide on a reversed-phase column, the analytical method itself should be stated.
- Identity by mass spectrometry. Expect confirmation consistent with the copper complex, including the copper isotope signature, or an explicit statement that the free peptide mass was measured after demetallation.
- Purity by RP-HPLC. A single dominant peak with the integration table shown. Copper peptides can tail on standard columns; a well-run method should still resolve the main peak cleanly.
- Appearance. Blue to blue-violet lyophilised solid. A white cake labelled GHK-Cu is a discrepancy worth querying.
- Batch traceability. A batch number on the vial that matches the certificate.
GenoPept publishes per-batch third-party certificates at /coa-certificates/. Our guide on how to read a peptide certificate of analysis explains each field in detail.
GHK-Cu in the GenoPept store
Frequently asked questions
What is the difference between GHK and GHK-Cu?
GHK is the free tripeptide glycyl-L-histidyl-L-lysine (C14H24N6O4, 340.38 Da, CAS 49557-75-7). GHK-Cu is the same peptide with one copper(II) ion chelated (C14H22CuN6O4, about 401.9 Da, CAS 89030-95-5). GHK is colourless in solution; GHK-Cu is deep blue. Much published cell-culture work describes GHK activity where copper from the medium is presumed to be bound in situ.
Why is GHK-Cu solution blue?
The blue colour comes from d–d electronic transitions of the copper(II) ion held in the peptide’s nitrogen coordination sphere. It is a direct visual indicator that the chelate is intact. A GHK-Cu solution that is pale, green-tinged or colourless suggests the copper has been displaced, precipitated or was never present at the expected ratio.
Does GHK-Cu need to be refrigerated?
Lyophilised GHK-Cu is normally stored refrigerated or frozen, kept dry, sealed and protected from light, which is the standard approach for lyophilised research peptides. Once reconstituted, solutions are far less stable and are typically refrigerated and treated as short-lived working material. Aliquoting on first reconstitution avoids repeatedly freezing and thawing the main stock.
What buffers are incompatible with GHK-Cu?
Strong chelators compete for the copper. EDTA, citrate and high concentrations of phosphate can strip or redistribute Cu(II), and markedly acidic conditions reprotonate the amide nitrogen that the chelate depends on. Near-neutral pH with weakly coordinating buffers preserves the complex. Any change of buffer is worth re-checking visually, since colour loss reports on dissociation immediately.
Who discovered GHK-Cu and when?
Loren Pickart isolated the GHK tripeptide from human plasma albumin fractions in 1973 while investigating a growth-modulating activity that differed between plasma from younger and older donors. Pickart and colleagues have since authored the major review literature on the compound, including papers in Oxidative Medicine and Cellular Longevity (2012), BioMed Research International (2015) and International Journal of Molecular Sciences (2018).
What is copper tripeptide-1?
Copper tripeptide-1 is the INCI cosmetic-ingredient name for GHK-Cu. The free peptide without copper is listed as tripeptide-1. The naming matters when cross-referencing cosmetic-science literature against biomedical papers, which use GHK-Cu, GHK:Cu(II) or “the tripeptide–copper complex glycyl-L-histidyl-L-lysine-Cu2+” for the same molecule.
What concentrations are used in published GHK-Cu cell studies?
Published fibroblast work reports activity in the picomolar-to-nanomolar range, with Maquart and colleagues (1988) describing collagen-synthesis stimulation at these very low concentrations. Reaching those levels from a milligram-per-millilitre laboratory stock requires several serial dilution steps, which is where most reproducibility error enters. This is research-context information about published methods only.
Is GHK-Cu the same as the GLOW and KLOW blends?
No. GHK-Cu is a single compound. GLOW is a multi-peptide research blend of BPC-157, TB-500 and GHK-Cu in one lyophilised vial; KLOW adds KPV. Blended vials require the total and per-component masses from the certificate of analysis to calculate any solution concentration, because the stated vial mass is the sum of several peptides.
References
- Pickart L, Vasquez-Soltero JM, Margolina A. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health. Oxidative Medicine and Cellular Longevity. 2012;2012:324832. PubMed
- Pickart L, Vasquez-Soltero JM, Margolina A. GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. BioMed Research International. 2015;2015:648108. PubMed
- Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. International Journal of Molecular Sciences. 2018;19(7):1987. PubMed
- Maquart FX, Pickart L, Laurent M, Gillery P, Monboisse JC, Borel JP. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Letters. 1988;238(2):343-346. PubMed
- Siméon A, Emonard H, Hornebeck W, Maquart FX. The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures. Life Sciences. 2000;67(18):2257-2265. PubMed
- Campbell JD, McDonough JE, Zeskind JE, et al. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Medicine. 2012;4(8):67. PubMed
- Canapp SO Jr, Farese JP, Schultz GS, et al. The effect of topical tripeptide-copper complex on healing of ischemic open wounds. Veterinary Surgery. 2003;32(6):515-523. Publisher
- National Center for Biotechnology Information. PubChem compound summaries: glycyl-L-histidyl-L-lysine (CID 73587) and its copper complex. PubChem
Research-grade GHK-Cu, batch-verified
GenoPept supplies GHK-Cu as a lyophilised copper tripeptide with a per-batch third-party certificate of analysis covering HPLC purity and mass-spectrometric identity, dispatched from the UK, strictly for laboratory research.