GHK-Cu (Copper Tripeptide-1): Research Guide

Identifiers

Common name

GHK-Cu

Also written

Copper tripeptide-1 · copper peptide · GHK copper

Peptide sequence

Glycyl-L-histidyl-L-lysine (Gly-His-Lys)

Compound class

Copper(II) complex of a tripeptide

Free tripeptide, GHK

C₁₄H₂₄N₆O₄, ≈340.4 g/mol (PubChem CID 73587)

Copper complex, GHK-Cu

C₁₄H₂₃CuN₆O₄⁺, ≈402.9 g/mol (PubChem CID 71587328)

First recovered from human plasma

Pickart, Thaler and Millard, Journal of Chromatography, 1979 (PMID 546910) — copper and iron co-isolated with it

Nomenclature note

Copper tripeptide-1 is recorded by PubChem as an INCI designation for the same complex. A naming convention is not an approval

Regulatory status

Not approved as a medicine by any regulator, in any jurisdiction

Supplied by Prime Peptides UAE as

100mg research pen — GHK-Cu product page

Two compounds share this name, and confusing them makes the literature unreadable

GHK is the free tripeptide: glycine, L-histidine, L-lysine, in that order. PubChem records it as C₁₄H₂₄N₆O₄ under CID 73587. GHK-Cu is that same tripeptide coordinated to a copper(II) ion, recorded separately as C₁₄H₂₃CuN₆O₄⁺ under CID 71587328. Two database entries, because they are two compounds.

This is not pedantry, and there is a published case that proves it. Siméon and colleagues (Life Sciences, 2000, PMID 11045606) measured an increase in matrix metalloproteinase-2 in fibroblast culture and reported it as attributable to the copper ion rather than to the peptide alone. A finding reported for the complex does not automatically transfer to the free tripeptide. Where the sources below studied one object rather than the other, this guide says which.

Terms of this kind are collected in the research peptide terminology glossary.

Why the copper is the point

Pickart and colleagues reported in Nature in 1980 (PMID 7453802) that the tripeptide readily forms complexes with copper(II) and increases uptake of the metal into cultured cells. Pickart followed it in In Vitro in 1981 (PMID 7021400) with the proposition that the tripeptide functions as a transporter of transition metals — copper in particular — to the cell surface for uptake.

That is the mechanistic claim the whole field rests on: a very small peptide that binds copper and moves it. And copper is a cofactor for a number of human enzymes, which is why the copper-binding property, rather than the peptide sequence on its own, is what the literature is organised around.

There is a corroborating detail in the earliest analytical work. When Pickart, Thaler and Millard recovered the tripeptide from human plasma in 1979 (PMID 546910), copper and iron came out with it — an early indication that the metal association is intrinsic to the molecule rather than an artefact of the assay.

What the published literature has examined

Recovery from human plasma, with the metals attached, 1979

Pickart, Thaler and Millard, Journal of Chromatography (PMID 546910). An analytical-chemistry paper on how transition metals affect recovery of the tripeptide from human plasma. This is the correct citation for where the sequence was originally found, and the earliest evidence that the metal association is intrinsic — copper and iron co-isolated with the peptide during isolation.

Copper uptake into cultured cells, 1980

Pickart, Freedman, Loker and colleagues, Nature (PMID 7453802). Reported that the tripeptide forms complexes with copper(II) and increases uptake of the metal into cultured hepatoma cells. This is the paper the copper-transport account rests on.

The tripeptide as a metal transporter, 1981

Pickart, In Vitro (PMID 7021400). Set out the proposition that the tripeptide functions as a transporter of transition metals, copper in particular, to the cell surface.

Collagen synthesis in fibroblast culture, 1988

Maquart, Pickart, Laurent and colleagues, FEBS Letters (PMID 3169264). Measured collagen synthesis in cultured fibroblasts exposed to the copper complex, and reported stimulation of collagen synthesis with no effect on cell proliferation — a distinction worth keeping, because the two are routinely collapsed in secondary commentary. The authors also noted that the GHK sequence occurs within collagen itself, and proposed that it may be released during tissue breakdown. The molar concentration range stated in that paper is deliberately not reproduced here.

Redox chemistry with ferritin, 1990

Miller, DeSilva, Pickart and Aust, Advances in Experimental Medicine and Biology (PMID 2244543). Examined the copper complex in relation to iron-catalysed lipid peroxidation, proposing an interaction with the ferritin channels involved in iron release. This entry sits outside the matrix-biology thread and is included because a guide that reports one thread of a literature is reporting a selection.

The one in-vivo study, 1993

Maquart, Bellon, Chaqour and colleagues, Journal of Clinical Investigation (PMID 8227353). A rat study using an implanted mesh chamber model. Chamber contents were analysed for dry weight, total protein, collagen, DNA, elastin, glycosaminoglycans, and messenger RNA for collagens and transforming growth factor beta. The paper reports increases in extracellular matrix measures and in type I and type III collagen messenger RNA, no increase in transforming growth factor beta messenger RNA, and no significant effect from a control tripeptide. The null finding and the control comparison are stated alongside the positive ones because that is what makes this a summary rather than a selection.

Matrix-remodelling enzymes in fibroblast culture, 2000

Siméon, Emonard, Hornebeck and Maquart, Life Sciences (PMID 11045606). Measured matrix metalloproteinase-2 in fibroblast culture medium and found it increased along with the corresponding messenger RNA — and attributed the increase to the copper ion rather than to the peptide alone. The same paper reports increased secretion of the tissue inhibitors TIMP-1 and TIMP-2. The authors’ own framing is that the complex acts on both the production side and the remodelling side of connective-tissue biology, not on one alone.

Where this literature is thin, stated plainly

Three characteristics of the GHK-Cu evidence base are easy to verify, rarely stated, and change how everything above should be read.

1. It is overwhelmingly cell culture and animal work. Seven of the eight papers above used cultured cells; one used rats. That is not a criticism — it is the correct design for the questions they asked — but it is the single most important qualifier on the whole record.
2. A large share of the primary literature involves one research group. Loren Pickart is an author on five of the eight entries. Independent replication by unrelated groups is thinner than this compound’s citation count suggests.
3. The most-quoted sources on this compound are review articles, not primary papers. Reviews are legitimate documents, but a review summarising a cell-culture literature does not create a stronger evidence base than the cell-culture literature it summarises. This guide cites the primary papers directly so a reader can see the experimental systems for themselves.

Regulatory status

GHK-Cu is not approved as a medicine by any regulator, in any jurisdiction, for any indication.

Copper tripeptide-1 is recorded by PubChem as an INCI designation for the same copper complex. INCI is a naming system: it standardises what an ingredient is called and establishes nothing about approval, permission or suitability for any application.

Prime Peptides UAE supplies GHK-Cu as a research material only. It is not supplied as a medicine and it is not supplied as a cosmetic.

What this literature does not establish

Published research attaches to a compound. It does not attach to a vial.

1. A cell-culture finding is a cell-culture finding. Collagen synthesis measured in cultured fibroblasts is a measurement in cultured fibroblasts. Extending it to any other system is an inference the cited papers do not make.
2. Findings reported for the complex are not findings about the free tripeptide. The 2000 paper attributes its principal measurement to the copper ion specifically.
3. A concentration of independent authorship is a limitation, and it belongs in any honest reading of this evidence base.
4. A published paper says nothing about a research material’s provenance — how to read a peptide COA.

How Prime Peptides UAE documents GHK-Cu

Common questions

References

All identifiers verified against the PubMed and PubChem records.

1. Pickart L, Thaler MM, Millard M. Journal of Chromatography. 1979;175(1):65–73. Transition-metal interference in recovering the tripeptide from human plasma. PMID 546910 · DOI 10.1016/s0021-9673(00)86403-1
2. Pickart L, Freedman JH, Loker WJ, et al. Nature. 1980;288(5792):715–717. Copper(II) complex formation and metal uptake into cultured cells. PMID 7453802 · DOI 10.1038/288715a0
3. Pickart L. In Vitro. 1981;17(6):459–466. The tripeptide as a transporter of transition metals to the cell surface. PMID 7021400 · DOI 10.1007/BF02633506
4. Maquart FX, Pickart L, Laurent M, et al. FEBS Letters. 1988;238(2):343–346. Collagen synthesis in fibroblast culture exposed to the copper complex. PMID 3169264 · DOI 10.1016/0014-5793(88)80509-x
5. Miller DM, DeSilva D, Pickart L, Aust SD. Advances in Experimental Medicine and Biology. 1990;264:79–84. The copper complex and iron-catalysed lipid peroxidation; proposed ferritin channel interaction. PMID 2244543 · DOI 10.1007/978-1-4684-5730-8_11
6. Maquart FX, Bellon G, Chaqour B, et al. Journal of Clinical Investigation. 1993;92(5):2368–2376. Rat implanted mesh chamber model; extracellular matrix, collagen and messenger RNA measures, with a control tripeptide comparison. PMID 8227353 · DOI 10.1172/JCI116842
7. Siméon A, Emonard H, Hornebeck W, Maquart FX. Life Sciences. 2000;67(18):2257–2265. Matrix metalloproteinase-2 and TIMP-1/TIMP-2 in fibroblast culture; copper-ion attribution. PMID 11045606 · DOI 10.1016/s0024-3205(00)00803-1
8. PubChem CID 73587 — glycyl-L-histidyl-L-lysine (GHK).
9. PubChem CID 71587328 — GHK-Cu, including the recorded Copper tripeptide-1 [INCI] synonym.

Related

• GHK-Cu product page — format, strength, AED price, document status
• KLOW Blend component reference — GHK-Cu is a named component
• How to read a peptide COA
• Testing and Quality