GHK-Cu — Molecular Weight, Formula, Sequence & Research Reference

01What is GHK-Cu?

GHK is a naturally occurring human tripeptide — glycine, histidine, lysine — present in plasma, saliva and urine, whose plasma concentration declines with age. Its defining chemical property is a very high affinity for copper(II): the histidine imidazole and the peptide backbone together form a square-planar chelate, and it is this complex, GHK-Cu, that most of the published dermatology and wound-healing literature actually studies.

That distinction is where the molecular weight confusion comes from. Four numbers circulate and each is correct for a different species: 340.38 g/mol is the free tripeptide (C14H24N6O4); 401.91 g/mol is the neutral 1:1 copper complex (C14H22CuN6O4), in which copper binding displaces two protons; roughly 403.93 g/mol appears when the complex is calculated naively as GHK plus a copper atom without accounting for that deprotonation; and 860.39 g/mol is prezatide copper acetate, the salt form. The 403.9 figure widely reprinted across peptide references — including, until this revision, our own hub table — is an arithmetic artefact rather than a measured mass.

GHK-Cu is also the clearest case in the library of research context mattering more than a data point. The substantial body of work on it is topical and in vitro. Systemic pharmacokinetics for administered GHK-Cu are not established, and no peer-reviewed human plasma half-life was located for either form.

02Molecular information

03Amino acid sequence

Structural modifications

None on the peptide backbone: free N-terminal amine, free C-terminal carboxylate, all three residues are standard L- (glycine is achiral). No amidation, acetylation, disulfide or cyclisation. The only 'modification' is metal coordination: in GHK-Cu a single Cu(II) ion is chelated in square-pyramidal geometry, with the three equatorial nitrogen donors being the glycine alpha-amino nitrogen, the deprotonated glycyl-histidyl backbone amide nitrogen, and the histidine imidazole nitrogen; the apical site is occupied by labile ligands (water or symmetry-related residues). The lysine side chain is not a copper donor. Chelation therefore involves loss of two peptide protons, which is why the complex formula is C14H22CuN6O4 rather than C14H24CuN6O4.

04Pharmacokinetic information

Half-life context

This is a genuine data gap, not an omission. The two major reviews of the compound (Pickart & Margolina, Int J Mol Sci 2018; Cosmetics 2018) report no absorption, distribution, elimination or half-life parameters at all, and note only that the peptide is susceptible to degradation by carboxypeptidase enzymes. The overwhelming majority of the literature concerns topical or in vitro application, where systemic pharmacokinetics were never measured. What IS documented is a steady-state endogenous plasma concentration and its decline with age: approximately 200 ng/mL (~1e-7 M) at age 20 falling to approximately 80 ng/mL by age 60. That is a concentration, not a half-life, and it describes endogenous GHK generated continuously from collagen proteolysis - it cannot be used to infer the disposition of exogenously applied GHK-Cu. Numerous vendor and blog pages quote specific half-life figures (values in the range of roughly one to several hours are commonly asserted); none of these trace to a retrievable primary pharmacokinetic study and they should be treated as unsourced. Distinguish three things that are frequently conflated: (a) plasma half-life of exogenous GHK-Cu - not established in any species from the sources retrieved; (b) residence time of topically applied GHK-Cu in skin - formulation-dependent and not expressible as a single number; (c) duration of downstream gene-expression and matrix-remodelling effects - reported over days to weeks in cell and animal studies, which is an effect duration and not a pharmacokinetic parameter.

05Research focus

Primary research areas

• cutaneous wound healing and matrix remodelling
• copper(II) chelation and transport
• collagen and glycosaminoglycan synthesis in fibroblasts
• gene-expression modulation (Connectivity Map analyses)
• topical cosmetic anti-ageing formulation
• antioxidant and anti-inflammatory signalling in vitro

Research context

GHK is an endogenous human tripeptide, glycyl-L-histidyl-L-lysine, first isolated from human plasma in 1973 and structurally identified by 1977 [1]. The sequence is present in the alpha-2(I) chain of type I collagen and is understood to be liberated by proteolysis at sites of tissue injury, which is the proposed basis for its description as a matrix-derived signalling fragment [1]. GHK binds Cu(II) with high affinity; isothermal titration calorimetry gives an association constant of approximately 7.0 x 10^14 M^-1, and structural work shows square-pyramidal coordination in which the glycine alpha-amino nitrogen, the deprotonated Gly-His backbone amide nitrogen, and the histidine imidazole nitrogen occupy the equatorial plane, with labile ligands at the apex [2]. This chelation is what defines GHK-Cu as a distinct species from the free peptide, and the reviews argue that complexation attenuates the redox reactivity of free copper ion [1]. Endogenous plasma GHK is reported at roughly 200 ng/mL at age 20, declining to roughly 80 ng/mL by age 60 [1]. Investigation has been overwhelmingly preclinical. In vitro work has used human dermal fibroblasts (collagen, elastin and glycosaminoglycan synthesis), COPD lung fibroblasts (TGF-beta pathway), and various tumour cell lines [1][3]. Animal models have included rabbit and rat wound-healing and ischaemic-wound models, murine acute lung injury, and a rat anterior cruciate ligament reconstruction model in which GHK-Cu produced a healing benefit the authors themselves characterised as transient [4]. Mechanistic claims rest largely on gene-expression profiling: Connectivity Map analyses are reported to show GHK altering expression of a large fraction of assayed human genes, with effects attributed to NF-kappaB suppression, integrin signalling, ubiquitin-proteasome activation and antioxidant gene induction [1][3]. Human data are confined almost entirely to topical cosmetic use. The 2018 review describes 12-week facial and eye-cream trials in cohorts of roughly 41 to 71 women reporting improvements in skin density, wrinkle appearance and photodamage [1]. The Cosmetic Ingredient Review Expert Panel assessed copper tripeptide-1 as safe at the concentrations then in cosmetic use, typically 0.00002 to 0.001 percent [5].

06Research evidence and limitations

Regulatory status

Not an FDA-approved drug in the United States for any indication, and no EMA marketing authorisation was identified. It is an established cosmetic ingredient: 'Copper Tripeptide-1' is an INCI-listed ingredient and the Cosmetic Ingredient Review Expert Panel concluded in its June 2014 final report that tripeptide-1 and its metal salts, including copper tripeptide-1, are safe in the then-current practices of use and concentration in cosmetics (reported use 0.00002-0.001 percent) [5]. Prezatide copper acetate is registered in FDA's Global Substance Registration System (UNII A3LEI4P1NB) and NCATS records it as possibly marketed outside the US in cosmetic products. In the US compounding context, GHK-Cu was nominated as a bulk drug substance for use under section 503A but the nomination was withdrawn by the nominator; FDA's associated commentary cited possible immunogenicity risk from aggregation and peptide-related impurities and limited human data. It does not currently appear on FDA's Category 2 table of bulk drug substances that may present significant safety risks. GHK-Cu is not named on the WADA Prohibited List.

07Research material and sourcing notes

Reported research-use reconstitution information

Manufacturer technical documentation (MedChemExpress datasheet HY-P0063, Copper tripeptide / GHK-Cu, research-use-only): solubility in water 50 mg/mL (124.41 mM), stated to require ultrasonication to dissolve fully. No buffer, pH or co-solvent specification is given on that datasheet, and no independent peer-reviewed solubility determination was retrieved. Crystallographic work (Mehr et al., Acta Cryst D 2020) prepared Cu(II)-GHK from equimolar peptide and copper and notes that copper binding is sensitive both to solution pH and to competing chelators in the buffer, so buffers containing strong metal chelators (e.g. EDTA) or high phosphate should be avoided when the intact complex is required. Laboratory handling information only; no dosing guidance is given or implied.

Reported storage and stability information

Manufacturer technical documentation (MedChemExpress HY-P0063): lyophilised powder -80 C for 2 years or -20 C for 1 year; stock solution -80 C for 6 months or -20 C for 1 month; sealed storage, protected from moisture and light. No peer-reviewed stability study for GHK-Cu was retrieved, and no manufacturer-documented in-use stability at 2-8 C or ambient temperature was found. Source type: supplier technical datasheet, not a pharmacopoeial or regulatory specification.

Identity and sourcing notes

The single largest identity hazard is that 'GHK' and 'GHK-Cu' are different substances and are routinely used interchangeably in commerce. Material labelled 'GHK' at 340.38 g/mol is the free tripeptide and contains no copper; material labelled 'GHK-Cu' should carry a copper assay. A COA should state explicitly which species is supplied, the counter-ion (free base, acetate, or TFA - TFA residue from reverse-phase purification is common in synthetic peptides and is not always declared), the copper:peptide stoichiometry, and hydration state. Because the three circulating molecular weights (340.38, 401.91, 403.93) differ by up to 18 percent, a COA that quotes a mass without naming the form makes molar concentration calculations unreliable. Copper content should be verified analytically (e.g. ICP-MS or AAS) rather than inferred from the label, since a nominally complexed product can be a physical mixture of free peptide and a copper salt; UV-visible spectroscopy of the characteristic Cu(II)-peptide d-d absorption is a useful orthogonal identity check, and the complex is visibly deep blue. Peptide identity and purity should be supported by RP-HPLC with a stated purity threshold and by mass spectrometry, noting that MS of the complex may show the free peptide ion depending on ionisation conditions. Note also the naming overlap with AHK-Cu, a different copper tripeptide sometimes marketed under confusingly similar 'copper peptide' language. Informational only.

08References and evidence

Primary sources

1. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene DatareviewPickart L, Margolina A — International Journal of Molecular Sciences, 2018;19(7):1987
2. The copper(II)-binding tripeptide GHK, a valuable crystallization and phasing tag for macromolecular crystallographyprimary literatureMehr A, Henneberg F, Chari A, Gorlich D, Huyton T — Acta Crystallographica Section D, 2020;76:1222-1232
3. Skin Regenerative and Anti-Cancer Actions of Copper PeptidesreviewPickart L, Margolina A — Cosmetics, 2018;5(2):29
4. Tripeptide-copper complex GHK-Cu (II) transiently improved healing outcome in a rat model of ACL reconstructionprimary literatureFu SC, Cheuk YC, et al. — Journal of Orthopaedic Research, 2015 (PMID 25731775)
5. Safety Assessment of Tripeptide-1, Hexapeptide-12, their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in CosmeticsregulatoryCosmetic Ingredient Review Expert Panel (Bergfeld WF, chair; Johnson W, author) — Cosmetic Ingredient Review, final report 30 June 2014

Chemical and molecular databases

• PubChem CID 73587 (glycyl-L-histidyl-L-lysine, free tripeptide)
• PubChem CID 378611 (Cu-GHK)
• ChEBI:75430 (Gly-His-Lys) - average 340.384, monoisotopic 340.18590
• FDA GSRS / precisionFDA UNII 39TG2H631E (PREZATIDE)
• NCATS Inxight Drugs - PREZATIDE COPPER ACETATE (UNII A3LEI4P1NB)
• DrugBank DBSALT002420 (prezatide copper acetate)
• MedChemExpress HY-P0063 technical datasheet (supplier documentation - solubility and storage only)
• ChemicalBook CAS 89030-95-5 (supplier aggregator - alternate protonation formula C14H21CuN6O4 / 400.91)

09Related compounds

• KPVAnother short endogenous-fragment tripeptide studied in vitro and in rodent models for anti-inflammatory and mucosal/skin repair endpoints.Reference page in preparation
• BPC-157Frequently grouped with GHK-Cu in the tissue-repair peptide literature, though its evidence base is likewise almost entirely rodent.
• TB-500 (as Thymosin β4)Endogenous peptide investigated in overlapping wound-healing, angiogenesis and matrix-remodelling models.
• Thymosin β4 FragmentShort active fragment of the same parent protein, studied on the same dermal repair endpoints as GHK-Cu.Reference page in preparation
• GlutathioneLike GHK-Cu, a small endogenous molecule whose redox and metal-handling chemistry underlies its investigated antioxidant role.Reference page in preparation

10Frequently asked questions