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Hydrogels for Osteochondral
Tissue Engineering
Journal of Biomedical

(March 2020)
Anti-Wrinkle Activity
& Transdermal Delivery
of GHK Peptide
Journal of Peptide Science
(March 2020)
Pulsed Glow Discharge
to GHK-Cu Determination
International Journal
of Mass Spectrometry

(March 2020)
Protective Effects of GHK-Cu
in Pulmonary Fibrosis
Life Sciences
(January 2020)
Anti-Wrinkle Benefits
of GHK-Cu Stimulating
Skin Basement Membrane
International Journal of Molecular Sciences
(January 2020)
Structural Analysis
Molecular Dynamics of
Skin Protective
TriPeptide GHK
Journal of Molecular Structure
(January 2020)
In Vitro / In Vivo Studies
pH-sensitive GHK-Cu in
Superabsorbent Polymer
GHK Enhances
Stem Cells Osteogenesis
Acta Biomaterialia
Antibacterial GHK-Cu
Nanoparticles for
Wound Healing
Particle & Particle (2019)
Effect of GHK-Cu
on Stem Cells and
Relevant Genes
OBM Geriatrics
GHK Alleviates
Neuronal Apoptosis Due
to Brain Hemorrhage
Frontiers in Neuroscience
Endogenous Antioxidant
International Journal of Pathophysiology and Pharmacology (2018)
Regenerative and
Protective Actions of
GHK-Cu Peptide
International Journal of
Molecular Sciences
Skin Regenerative and
Anti-Cancer Actions
of Copper Peptides
GHK-Cu Accelerates
Scald Wound Healing
Promoting Angiogenesis
Wound Repair and

GHK Peptide Inhibits
Pulmonary Fibrosis
by Suppressing TGF-β1
Frontiers in Pharmacology
Skin Cancer Therapy
with Copper Peptides
The Effect of Human
Peptide GHK Relevant to
Nervous System Function
and Cognitive Decline
Brain Sciences (2017)
Effects of Tripeptide
GHK in Pain-Induced
Aggressive Behavior
Bulletin of Experimental
Biology & Medicine
GHK-Cu Elicits
In Vitro Alterations
in Extracellular Matrix
Am Journal of Respiratory
and Critical Care Medicine

Selected Biomarkers &
Copper Compounds
Scientific Reports

GHK-Cu on Collagen,
Elastin, and Facial Wrinkles
Journal of Aging Science
Tri-Peptide GHK-Cu
and Acute Lung Injury

Effect of GHK Peptide
on Pain Sensitivity
Experimental Pharmacology

New Data of the
Cosmeceutical and
TriPeptide GHK
SOFW Journal
GHK Peptide as a
Natural Modulator of
Multiple Cellular Pathways
in Skin Regeneration
BioMed Research (2015)
Resetting Skin Genome
Back to Health
Naturally with GHK
Textbook of Aging Skin
GHK-Cu May Prevent
Oxidative Stress in Skin
by Regulating Copper and
Modifying Expression of
Numerous Antioxidant Genes Cosmetics (2015)
GHK Increases
TGF-β1 in
Human Fibroblasts

Acta Poloniae

The Human Skin Remodeling Peptide Induces Anti-Cancer
Expression and DNA Repair Analytical Oncology
Resetting the
Human Genome to Health
BioMed Research
Enhanced Tropic Factor Secretion of Mesenchymal
Stem Cells with GHK
Acta Biomater
Anxiolytic (Anti-Anxiety)
Effects of GHK Peptide
Bulletin of Experimental
Biology & Medicine
Lung Destruction and
its Reversal by GHK
Genome Medicine
TriPeptide GHK Induces
Programmed Cell Death
of Neuroblastoma
Journal of Biotechnology
Stem Cell
Recovering Effect
of GHK in Skin
Peptide Science
Skin Penetration of
Copper Tripeptide in Vitro
Journal of International
Inflammation Research
Possible Therapeutics
for Colorectal Cancer
Journal of Clinical and
Experimental Metastasis
Methods of Controlling
Differentiation and
Proliferation of Stem Cells
Effects of
Copper Tripeptide
on Irradiated Fibroblasts
American Medical Association
Avoid Buying Fake Copper Peptides Dangerous














References on Chemistry of GHK-Cu

Discovery of GHK A tripeptide in human plasma that increases the survival of hepatocytes and the growth of hepatoma cells,. Pickart Ph.D. Thesis in Biochemistry, University of California, San Francisco, 1973
Discovery of GHK Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Pickart and Thaler (University of California, San Francisco, USA) Nature New Biol 1973 May 16;243(124):85-7 
Purification of GHK by development of a high pressure chromatograghic method. Methods were developed for the purification of peptides and proteins by high pressure chromatography. This may have been the first paper to describe this method which is now widely used.  A rapid method for the purification of histones and a variety of growth- promoting proteins and peptides by chromatography on silica gel was developed. Insulin, albumin, somatomedins, and histones were purified on high-pressure silica gel columns.  Purification of growth promoting peptides and proteins, and of histones, by high pressure silica gel chromatography.  Pickart and Thaler  (University of California, San Francisco, USA) Prep Biochem 1975, 5:397-412
Determination of tripeptide structure. Chromatographic evidence has suggested that tripeptide was Gly-His-Lys. Chemical analysis found structure to be Gly-His-Lys  Growth modulating serum tripeptide is glycyl-histidyl-lysine. Schlesinger, Pickart and Thaler  (Harvard University) Experientia 1977, 33(3):324-5
Development of improved methods of isolation of GHK from plasma and the co-isolation of copper(2+) and iron (2+) with GHK. Analysis of GHK isolates for metals. During the isolation of GHK-Cu from human plasma, copper and iron were found to co-isolate with the peptide. Studies with [3H]GHK demonstrated that copper and iron interfered at several steps of the procedure for the isolation of GHK from plasma (gel filtration chromatography, high pressure silica gel columns). Removal of these metals with an insoluble chelating resin (Cellex 100) enhanced recovery of [3H]GHL from plasma 8-fold.  Effect of transition metals on recovery from plasma of the growth- modulating tripeptide glycylhistidyllysine. Pickart, Thaler and Millard  (University of California, San Francisco, USA, US Dept. Agriculture  Lab, Albany, CA, USA) J Chromatogr 1979  11;175(1):65-73

Studies on GHK and structure and activity. A variety of GHK-Cu analogs were synthesized and tested for their stimulation of DNA synthesis.

While many analogs similar to GHK-Cu had bioactivity, none equaled the bioactivity of GHK-Cu

Growth modulating human plasma tripeptide: Relationship between molecular structure and DNA synthesis in hepatoma cells. Pickart and Thaler  FEBS Lett 1979, 104(1):119-22
Cell culture studies of the effects of GHK complexed with copper and iron on cell growth patterns. Experimental observations that GHK is complexed with the transition metal ions Cu++ and Fe++ in vivo and may exert its biological effects as a peptide-metal chelate.At physiological pH in vitro, GHK associates with ionic copper, cobalt, iron, molybdenum, manganese, nickel, and zinc, but has no affinity for calcium, manganese, potassium, and sodium. GHK acts synergistically with copper, iron, cobalt, and zinc to alter patterns of cell growth in monolayer cultures. These transition metals induce cellular flattening and adhesion to support surfaces, and inhibit DNA synthesis and lactic acid production when growth is limited by reduction of serum concentrations in medium. These inhibitory effects are neutralized, and intercellular adhesion and growth are stimulated by GHK in medium at nanomolar concentrations. Cu and Fe are the most active metals when combined with GHK. GHK and transition metals, which appear to form complexes prior to interaction with cells. Growth modulating tripeptide (glycylhistidyllysine): association with copper and iron in plasma, and stimulation of adhesiveness and growth of hepatoma cells in culture by tripeptide-metal ion complexes. Pickart and Thaler  (University of California, San Francisco, USA) J Cell Physiol 1980, 102(2):129-39
GHK and copper(II) transport into cells.  The association of GHK with copper and a homology similarity between the tripeptide and the copper transport sites on albumin and alpha- fetoprotein, where the cupric atom is bound to a histidyl residue adjacent to a basic residue, suggested that GHK may act as a copper transport factor.It was found that GHK readily forms complexes with copper(II) and enhances the uptake of the metal into cultured cells. Growth modulating plasma tripeptide may function by facilitating copper uptake into cells. Pickart, Freedman, Loker, Peisach, Perkins, Stenkamp and Weinstein Nature 1980, 288, 715-7
A review of information on the biological actions and structure function relationships as understood in 1981.  At this time GHK's chemoattractant actions on white cells were unknown. Glycylhistidyllysine (GHK), a tripeptide from human plasma, has been shown to alter the growth rate of many cell types and organisms in culture systems. GHK is optimally active at concentrations between 10 and 200 nanograms/milliliter. Present information suggests that GHK functions as a transporter of transition metals, in particular copper, to the cell surface for uptake into the cell.  The use of glycylhistidyllysine in culture systems.  Pickart  In Vitro 1981,17(6):459-66
Determination of the effectiveness of GHK chelation for copper under physiological conditions. The interaction between Cu(II) and the growth modulating tripeptide GHK in the presence and absence of L-histidine was investigated by potentiometric titration and visible-absorption spectrophotometry at 25 degrees C in 0.15 M-NaCl. Analyses in the pH range 3.5-10.6 indicated the presence of multiple species in solution in the binary system and extensive amounts of the ternary complexes in the ternary system. The species distribution and the stability constants were evaluated.  The results obtained from the equilibrium dialysis experiments showed that GHK was able to compete with albumin for Cu(II) at pH 7.5. At equimolar concentrations of albumin and the peptide, about 42% of the Cu(II) was bound to the peptide. At the physiologically relevant concentrations of Cu(II), albumin, L-histidine and this peptide, about 6% of the Cu(II) was associated with the low- molecular-weight components.  The interaction of copper(II) and glycyl-L-histidyl-L-lysine, a growth- modulating tripeptide from plasma. Lau and Sarkar Biochem J 1981 199(3):649-56
Review of GHK-Metal Interactions Available evidence suggests that GHK acts as a complex with transition metals Peptide and protein complexes of transition metals as modulators of cell growth.  Pickart In: Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins (Marcel Dekker Pub.) 1982, 75-104. 
Interaction of Cu(II) and Gly-His-Lys was determined by 13C- and 1H-NMR and EPR spectroscopy. Interaction of Cu(II) and GHK, a growth-modulating tripeptide from plasma, was investigated by 13C- and 1H-NMR and EPR spectroscopy. The n.m.r. line-broadening was interpreted in terms of major and minor species formed as a function of pH. The NMR line-broadening was interpreted in terms of major and minor species formed as a function of pH. The EPR parameters in the medium pH range, A parallel = 19.5 mT and g parallel = 2.21, fit well with the contention that Cu(II) is ligated to Gly-His-Lys through one oxygen atom and three nitrogen atoms in a square-planar configuration. 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. Laussac JP; Haran R; Sarkar B Biochem J 1983 Feb 1;209(2):533-9
Magnetic resonance studies of GHK and copper Determine the stability of GHK-Cu in solution. GHK and GHK-Cu slowly exchange copper(II) in solution.  PMR studies of Cu(II) and Zn(II) interaction with glycyl-l-histidyl-l-lysine and related peptides. Kwa E, Bor-Sheng L, Rose N, Weinstein B, Pickart L.  Peptides 1983, 8, 805-808
Studies on the structure of GHK-Cu in solution. Optical, electron paramagnetic resonance, and electron spin-echo envelope spectroscopies were used to examine the structure of the Cu(II) complex of glycyl-L-histidyl-L-lysine (GHK) in solution.At neutral pH, GHK forms a mononuclear 1:1 Cu(II) compound having an EPR spectrum resembling that of Cu(II) equatorially coordinated by two or three  nitrogen atoms. Electron spin-echo studies demonstrate that one of these is located in the histidyl imidazole ring. A pH titration of Cu(II)-GHK shows three optical transitions with apparent pKs of 3.6, 9.2 and 11.4 and molecularities, with respect to protons, of 2, 2, and 1, respectively. At the lowest pK, GHK binds Cu(II), forming the species present at physiological pH. These solution studies are consistent with nitrogen  coordination of Cu(II) in Cu(II)-GHK. Structure of the glycyl-L-histidyl-L-lysine copper(II) complex in  solution.  Freedman, Pickart, Weinstein, Mims and Peisach (Albert Einstein Medical School, New York, USA)  Biochemistry 1982 21(19):4540-4


Determination of the X-ray structure of aqueous crystals  of GHK-Cu.


The structure of a copper complex of the growth factor glycyl-l-histidyl-l-lysine at 1.1 angstrom resolution.  Perkins CM, Rose NJ, Weinstein B, Stenkamp RE, Jensen, LH, Pickart L. Inorg. Chem Acta 1984, 82, 93-99.
Studies of cell inhibitory copper complexes A series of hydrophobic analogs of the GHL-Cu structure were synthesized and tested. Hydrophobic analogs of the GHL-Cu structure were inhibitory to cell DNA synthesis and growth Cytotoxic chelators and chelates inhibition of DNA synthesis in cultured rodent and human cells by aroylhydrazone analogs of the gly-l-his-l-lys copper(II) complex.  Johnson, Pickart and Rose Inorg Chem Acta 67, pp. 159-165, 1982
Synthesis of growth inhibitory analogs of GHK-Cu. A variety of copper binding growth inhibitory analogs of GHK-Cu very synthesized and tested. A variety of copper binding analogs of GHK-Cu had potent activity in the inhibition of fibroblasts and fibrosarcoma cells at concentrations of 10exp (-16) M.  Inhibition of the growth of cultured cells and an implanted fibrosarcoma by aroylhydrazone analogs of the Gly-His-Lys-Cu(II) complex. Pickart, Goodwin, Burgua, Murphy and Johnson Biochem Pharmacol 1983, 32(24):3868-71
A review of information on the biological actions and structure function relationships as understood in 1983.  At this time GHK's chemoattractant actions on white cells were unknown The biological effects and mechanism of action of the plasma tripeptide glycyl-l-histidyl-l-lysine.  Pickart Lymphokines 8, pp. 425-446, 1983
Electron spin resonance studies of the molecular action of growth inhibitory copper analogs of GHK-Cu with cells. The interaction of two cytotoxic hydrophobic GHK-Cu analogs SBH-Cu  (salicylaldehydebenzol hydrazone-Cu) and PCPH-Cu (pyridine 2-carboxyl aldehyde 2'-pyridyl hydrozonate-Cu) with cells was determined. SBH-Cu(II) and PCPH-Cu(II) first interact with sufhydyl groups in the cells. The Cu(II)  is first reduced to Cu(I), then re-oxidized to Cu(II) Formation of adducts between cupric complexes of known antitumor agents and ehrlich ascites cells.  Antholine, Lyman, Petering and Pickart (University of Wisconsin Milwaukee, USA) Biological and Inorganic Copper Chemistry, Adenine Press, pp. 125-137, 1985

GHK forms stable complexes with palladium (II) The binding of palladium by GHK was determined.

Conclusion: GHK may possibly participate in the transport of Pd(II) in the tissues and its elimination through the kidneys 

NMR studies on binary and ternary Pd(II) complexes formed by the growth modulating tripeptide glycylhistidyllysine and nucleotides.  Laussac, Pasdeloup and Hadjiliadis J Inorg Biochem 30:227-38, 1987
The authors characterized the mechanism of copper accumulation by the brain, using rat hypothalamic tissue slices incubated with 67Cu as a model system.Two ligand-dependent processes were discerned: a high affinity, low capacity process and a low affinity, high capacity process.  The two processes were similar in that each exhibited: (a) a requirement for complexing of copper for optimal 67Cu accumulation; and (b) a broad ligand specificity with respect to amino acids (histidine, cysteine, threonine, glycine) and peptides (Gly-His-Lys, glutathione) and ineffectiveness of albumin in serving as a facilitatory ligand. Brain tissue accumulates 67copper by two ligand dependent saturable processes. A high affinity, low capacity and a low affinity, high capacity process. Hartter and Barnea (Department of Obstetrics and Gynecology, University of Texas Health Science Center, Dallas, USA)  J Biol Chem 1988 Jan 15;263(2):799-805
Study of GHK degradation in rats A selective and sensitive high-performance liquid chromatographic (HPLC) method was developed for the determination of  GHK. and its metabolite, L-histidyl-L-lysine in rat plasma. The limit of detection for GHK and HK were 50 and 15 ng/ml, respectively, and the calibration curves were linear in the range 0.1-5.0 microg/ml. The developed method was applied to the pharmacokinetic study of GHK after a single dose was administered intravenously to rats. GHK was rapidly degraded to HK, which was eliminated rapidly. Simultaneous determination of glycyl-L-histidyl-L-lysine and its metabolite, L-histidyl-L-lysine, in rat plasma by high-performance liquid chromatography with post-column derivatization. Endo, Miyagi and Ujiie   (Pharmacological Laboratories, Kissei Pharmaceutical Co., Ltd., Minamiazumi, Nagano, Japan) J Chromatogr B Biomed Sci Appl 1997, 692(1):37-42

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