GHK-Cu Peptide

Reference

GHK-Cu molecular structure

GHK-Cu structure: the Gly-His-Lys sequence, how copper(II) is coordinated, formula and mass for each public record, and an interactive 3D model.

By the GHK-Cu Peptide editorial team · Last reviewed · Editorial review: pending

Short answer

GHK-Cu is the tripeptide Gly-His-Lys (C14H24N6O4, 340.38 g/mol) [PubChem] with copper(II) bound by the glycine amine, the deprotonated Gly–His amide nitrogen and a histidine imidazole nitrogen [Hureau 2011]. PubChem records the 1:1 complex as C14H23CuN6O4⁺, 402.92 g/mol [PubChem], but also holds other records under the same name with different formulas.

GHK-Cu Molecular Explorer

2D depiction of GHK from PubChem CID 73587. Choose a residue, or show the atoms reported to bind copper.

Skeletal structure of glycyl-L-histidyl-L-lysine (GHK)Glycine, histidine and lysine joined by two peptide bonds. Histidine carries an imidazole ring and lysine a four-carbon chain ending in an amine.OOHOONHNHNHNH₂NH₂N
Depiction coordinates: PubChem. Wedges show the two L-stereocentres.

Residues

GHK formula
C14H24N6O4
Mol. weight
340.38 g/mol
InChIKey
MVORZMQFXBLMHM-QWRGUYRKSA-N
PubChem
CID 73587

Copper coordination

Spectroscopy in the early 1980s established a mononuclear 1:1 complex at neutral pH with copper bound by two or three nitrogens, one in the imidazole ring [Freedman 1982], and EPR spectra between pH 6 and 9.6 showed the seven-line pattern of three coordinated nitrogens [Laussac 1983]. A 2011 X-ray and multi-spectroscopy study confirmed three nitrogen ligands in solution and a dimer in the crystal [Hureau 2011]. Potentiometric work found several species across pH 3.5–10.6 [Lau 1981], and the lysine side-chain amine joins only at alkaline pH [Conato 2001].

Schematic of the copper(II) coordination sphere in GHK-CuA copper ion at the centre with four equatorial binding positions: the glycine amine nitrogen, the deprotonated amide nitrogen of the Gly–His bond, a histidine imidazole nitrogen, and a labile oxygen. Schematic only; not drawn from atomic coordinates.Cu²⁺NN⁻NOGly amineGly–His amideHis imidazolelabile O

Schematic, not coordinates

  1. N: Glycine N-terminal amine (–NH₂) [Hureau 2011]
  2. N⁻: Deprotonated amide nitrogen of the Gly–His peptide bond [Hureau 2011]
  3. N: Histidine imidazole ring nitrogen [Freedman 1982]
  4. O: Labile oxygen: a carboxylate in the crystal, exchangeable in solution [Hureau 2011]

In the crystal the complex is a dimer; in solution it is a monomer whose fourth position is occupied by an exchangeable oxygen [Hureau 2011]. The lysine side-chain amine stays protonated at physiological pH and is not a ligand [Conato 2001]. No openly licensed crystal coordinates for GHK-Cu were found in the Crystallography Open Database, so this site does not render a 3D copper complex.

One name, several records

These are the PubChem records that list GHK-Cu or its registered names. They differ in formula, charge and copper ratio. The 1:1 record’s formula and +1 charge match the species the kinetic literature writes as Cu(H₋₁GHK)⁺ [Beuning 2018], while a 2:1 species also occurs and was among the forms that crossed a model membrane [Mazurowska 2007].

PubChem records for GHK and GHK-Cu
PubChem recordFormulaMass (g/mol)Net chargeHow to read it
CID 73587
glycyl-L-histidyl-L-lysine (GHK, prezatide)
CAS 49557-75-7 · UNII 39TG2H631E · INCI Tripeptide-1
C14H24N6O4340.380The copper-free peptide. The only one of the four with a computed 3D conformer. [PubChem]
CID 71587328
Prezatide copper
CAS 89030-95-5 · UNII 6BJQ43T1I9 · INCI Copper tripeptide-1
C14H23CuN6O4⁺402.92+1The 1:1 complex as a net +1 ion. The formula matches the species solution chemists describe, but the record draws copper as a separate ion with no Cu–N bonds, so it is not a coordination structure. [PubChem]
CID 139035031
Copper tripeptide (deprotonated-nitrogen depiction)
Also listed as “GHK-Cu”
C14H21CuN6O4⁻400.90-1Draws both the amide and the glycine amine as deprotonated, giving a net −1 ion. The amine deprotonation is not what the solution studies report at neutral pH. [PubChem]
CID 9831891
Bisprezatide copper (2:1)
CAS 130120-56-8 · also listed as “GHK-Cu”
C28H46CuN12O8742.30Two peptides per copper. A 2:1 species is reported in solution chemistry and among the forms that crossed a model membrane, so a label that says only “GHK-Cu” does not say which ratio is meant. [PubChem]

Reference data

GHK and GHK-Cu reference properties
PropertyValue
SequenceGly-His-Lys (GHK), all L-amino acids [PubChem]
IUPAC name (GHK)(2S)-6-amino-2-[[(2S)-2-[(2-aminoacetyl)amino]-3-(1H-imidazol-5-yl)propanoyl]amino]hexanoic acid [PubChem]
First identifiedAs a growth-modulating tripeptide in human serum (1977) [Schlesinger 1977]
XLogP3 (GHK)−4.4 (computed; very hydrophilic) [PubChem]
Topological polar surface area (GHK)176 Ų (computed) [PubChem]
H-bond donors / acceptors (GHK)6 / 7 (computed) [PubChem]
Rotatable bonds (GHK)11 (computed) [PubChem]
Cu(II) affinity at pH 7.4Conditional Kd 7.0 × 10⁻¹⁴ M, by isothermal titration calorimetry [Trapaidze 2012]
Solid-state structureDimeric Cu(II)–GHK in the crystal; monomeric in solution [Hureau 2011]
Forced degradationHydrolysis under basic and oxidative stress; three degradants by HPLC-MS, one is histidine [Badenhorst 2016]
Acid–base groupsGlycine amine and histidine imidazole titrate over the same pH range; the lysine amine titrates much higher [Rabenstein 1977]
Copper exchange rate (to GHK)1.6 × 10² M⁻¹ s⁻¹ from a model copper–peptide donor [Beuning 2018]

Related: GHK vs GHK-Cu · how identity and copper content are tested · mechanism of action.

Frequently asked questions

What is the molecular weight of GHK-Cu?

It depends on which form is meant. Copper-free GHK is 340.38 g/mol. The 1:1 complex recorded as prezatide copper is 402.92 g/mol, and the 2:1 bis-complex is 742.3 g/mol. Salt forms such as acetate add further mass.

What is the chemical formula of GHK-Cu?

PubChem records the 1:1 complex as C14H23CuN6O4 with a +1 charge (prezatide copper). Copper-free GHK is C14H24N6O4.

Which atoms bind the copper in GHK-Cu?

In solution at neutral pH: the glycine amine nitrogen, the deprotonated amide nitrogen between glycine and histidine, and a histidine imidazole nitrogen, with a labile oxygen in the fourth position.

Is there a crystal structure of GHK-Cu?

Yes. An X-ray structure published in 2011 shows a dimer in the solid state. We found no openly licensed copy of its coordinates, so this site shows a labelled schematic rather than a 3D copper complex.

References

  1. Rabenstein DL, Greenberg MS, Evans CA (1977). Determination of the microscopic and macroscopic acid dissociation constants of glycyl-L-histidyl-L-lysine and related histidine peptides. Biochemistry. PubMed 14668 · doi:10.1021/bi00624a026[Chemistry, grade D]
  2. Freedman JH, Pickart L, Weinstein B et al. (1982). Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution. Biochemistry. PubMed 6291585 · doi:10.1021/bi00262a004[Chemistry, grade D]
  3. Laussac JP, Haran R, Sarkar B (1983). N.m.r. and e.p.r. investigation of the interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma. Biochem J. PubMed 6303307 · doi:10.1042/bj2090533[Chemistry, grade D]
  4. Lau SJ, Sarkar B (1981). The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth-modulating tripeptide from plasma. Biochem J. PubMed 7340824 · doi:10.1042/bj1990649[Chemistry, grade D]
  5. Conato C, Gavioli R, Guerrini R et al. (2001). Copper complexes of glycyl-histidyl-lysine and two of its synthetic analogues: chemical behaviour and biological activity. Biochim Biophys Acta. PubMed 11325542 · doi:10.1016/s0304-4165(01)00127-1[Chemistry, grade D]
  6. Hureau C, Eury H, Guillot R et al. (2011). X-ray and solution structures of Cu(II) GHK and Cu(II) DAHK complexes: influence on their redox properties. Chemistry. PubMed 21780203 · doi:10.1002/chem.201100751[Chemistry, grade D]
  7. Trapaidze A, Hureau C, Bal W et al. (2012). Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine. J Biol Inorg Chem. PubMed 21898044 · doi:10.1007/s00775-011-0824-5[Chemistry, grade D]
  8. Beuning CN, Mestre-Voegtlé B, Faller P et al. (2018). Measurement of Interpeptidic Cu(II) Exchange Rate Constants by Static Fluorescence Quenching of Tryptophan. Inorg Chem. PubMed 29648796 · doi:10.1021/acs.inorgchem.8b00182[Chemistry, grade D]
  9. Mazurowska L, Mojski M (2007). ESI-MS study of the mechanism of glycyl-l-histidyl-l-lysine-Cu(II) complex transport through model membrane of stratum corneum. Talanta. PubMed 19071668 · doi:10.1016/j.talanta.2006.11.034[Chemistry, grade D]
  10. Schlesinger DH, Pickart L, Thaler MM (1977). Growth-modulating serum tripeptide is glycyl-histidyl-lysine. Experientia. PubMed 858356 · doi:10.1007/BF02002806[Chemistry, grade D]
  11. Badenhorst T, Svirskis D, Wu Z (2016). Physicochemical characterization of native glycyl-l-histidyl-l-lysine tripeptide for wound healing and anti-aging: a preformulation study for dermal delivery. Pharm Dev Technol. PubMed 25384620 · doi:10.3109/10837450.2014.979944[Chemistry, grade D]
  12. PubChem, National Library of Medicine. glycyl-L-histidyl-L-lysine (CID 73587). Source[retrieved 2026-11-11]
  13. PubChem, National Library of Medicine. Prezatide copper (CID 71587328). Source[retrieved 2026-11-11]
  14. PubChem, National Library of Medicine. Copper tripeptide, deprotonated-amine depiction (CID 139035031). Source[retrieved 2026-11-11]
  15. PubChem, National Library of Medicine. Bisprezatide copper (CID 9831891). Source[retrieved 2026-11-11]
  16. FDA Global Substance Registration System. PREZATIDE COPPER, UNII 6BJQ43T1I9. Source[retrieved 2026-11-11]