AHK-Cu: the other copper tripeptide

What AHK-Cu is

AHK-Cu is the copper(II) complex of the tripeptide L-alanyl-L-histidyl-L-lysine — three residues, Ala-His-Lys, coordinated to a copper ion. It is one of a small family of copper-binding tripeptides that appear in the cosmetic and hair-care literature, of which GHK-Cu is by a wide margin the most studied.

The structural relationship to GHK is exact and worth stating precisely: the sequences are Gly-His-Lys and Ala-His-Lys respectively, so the only difference is a methyl group on the first residue’s side chain. Both therefore present the same Xaa-His arrangement — an N-terminal amine, a peptide nitrogen and a histidine imidazole nitrogen — that is the anchor for square-planar copper(II) coordination in this family of peptides. The copper coordination chemistry of GHK, and of the related DAHK sequence from serum albumin, has been characterised structurally and thermodynamically (Hureau et al., 2011; Trapaidze et al., 2012). Those are studies of GHK and DAHK, not of AHK, and we cite them as motif chemistry rather than as data about this ingredient.

A single methyl group is a small change to a molecule and can be a large change to its behaviour. It is not a basis for transferring a body of evidence.

Reference data

The free tripeptide has a clean public record. The copper complex’s record needs a caveat, which is given below rather than hidden.

Two caveats on this table

First, the PubChem entry for the copper complex is deposited as “[L-Alanyl-N-L-histidyl-N,N3-L-lysinato(2-)]copper monohydrochloride” and its listed formula carries a net negative charge. It is a useful identity anchor for the CAS number, but it should not be treated as a definitive statement of the stoichiometry of a commercial material — copper-peptide complexes are supplied in varying salt and hydrate forms, and the copper content is something a certificate should state rather than something you should infer from a database.

Second, we could not find an assigned INCI name for AHK-Cu. GHK-Cu has one (Copper Tripeptide-1). For anyone formulating a product that must carry an INCI ingredient list, that is a practical obstacle independent of the chemistry, and it should be resolved before the ingredient goes into a development brief.

The literature, in full

This section is short because the literature is. We searched for the trade name, the peptide name in several forms and the sequence.

The one relevant study

Pyo et al. (2007, Arch Pharm Res), from the Department of Dermatology at Seoul National University, evaluated AHK-Cu on human hair growth ex vivo and on cultured dermal papilla cells. At 10⁻¹² to 10⁻⁹ M, the complex was reported to stimulate the elongation of human hair follicles ex vivo and the proliferation of dermal papilla cells. Flow cytometry with annexin V/propidium iodide labelling showed a reduction in apoptotic dermal papilla cells that the authors state was not statistically significant; the Bcl-2/Bax ratio was reported as elevated and cleaved caspase-3 and PARP as reduced at 10⁻⁹ M. The authors’ own framing is that the study “proposed” the mechanism.

What that study is: an independent academic ex-vivo and cell-culture experiment, at femtomolar-to-nanomolar concentrations, with one of its own endpoints failing significance. What it is not: a human trial, a topical study, a formulation study, or evidence of anything happening when the material is applied to a scalp in a product.

The other AHK paper

Jung et al. (2018, Differentiation) studied a vitamin-C-linker-conjugated AHK tripeptide and BMP-2-induced osteogenic differentiation in mouse C2C12 myoblasts. Different molecule (a conjugate), different tissue, different question. It is listed here for completeness rather than as relevant evidence.

What is missing

• No human trial of AHK-Cu, topical or otherwise.
• No skin or scalp permeability data.
• No Cosmetic Ingredient Review safety assessment that we could locate, and so no independently reviewed maximum use concentration.
• No published stability or formulation-compatibility study.
• No published head-to-head comparison against GHK-Cu, despite the two being routinely sold as interchangeable.

Formulation, stability and storage

Nothing is published on this ingredient specifically. What can be said follows from the fact that it is a copper complex, and is labelled as such.

• Copper is a redox-active metal. Copper(II) participates in redox chemistry and can catalyse the oxidation of other formulation components. Combining a copper peptide with an oxidation-sensitive active — ascorbic acid is the obvious one — is a known formulation conflict in this ingredient class, and is a reason copper peptides usually sit in their own product rather than in a kitchen-sink serum.
• Competing chelators. Anything else in the formula that binds copper competes for the metal. That includes ordinary chelating preservative-boosters such as EDTA, and it includes other peptides: Argireline has a measured affinity for copper(II), so combining the two is a real interaction rather than a theoretical one.
• Colour. Copper peptides are strongly coloured. That is a finished-product consideration, not a defect.
• pH. The coordination geometry of copper-peptide complexes is pH-dependent as general coordination chemistry. No pH window has been published for this specific material, so we do not state one.

As raw material, store dry, cold and dark. See how to store peptides.

Verifying identity and purity

Copper complexes need one check more than an ordinary peptide. Mass spectrometry confirms the peptide identity — approximately 354 Da for the free Ala-His-Lys tripeptide — and HPLC reports purity. On top of that, the copper content and stoichiometry are part of what makes the material reproducible, and a certificate that reports peptide purity without saying anything about copper has answered only half the question. The same point applies to GHK-Cu.

See how to read a COA and how to verify peptide purity; batches we ship are on verify.

Sourcing and related ingredients

Supplied as raw material with a per-batch Certificate of Analysis. Not supplied as a finished cosmetic, and a certificate is not a cosmetic safety assessment.

The comparison that matters is GHK-Cu, one residue away and with a genuinely substantial published literature behind it. Acetyl Tetrapeptide-3 and Matrixyl 3000 both contain the same His-Lys-bearing motif in uncomplexed form. Everything in the cluster is listed on the cosmetic ingredient hub.

Frequently asked questions

Literature cited

1. Pyo HK, Yoo HG, Won CH, et al. “The effect of tripeptide-copper complex on human hair growth in vitro.” Arch Pharm Res. 2007;30(7):834–839. PMID 17703734. pubmed.ncbi.nlm.nih.gov/17703734. (Ex vivo and cell culture, 10⁻¹²–10⁻⁹ M; the apoptosis reduction was not statistically significant.)
2. Jung JI, et al. “Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells.” Differentiation. 2018. PMID 29567599. pubmed.ncbi.nlm.nih.gov/29567599. (A conjugate, in a different tissue; listed for completeness.)
3. Hureau C, Eury H, Guillot R, et al. “X-ray and solution structures of Cu(II) GHK and Cu(II) DAHK complexes: influence on their redox properties.” Chemistry. 2011;17(36):10151–10160. PMID 21780203. pubmed.ncbi.nlm.nih.gov/21780203. (Motif coordination chemistry — GHK and DAHK, not AHK.)
4. Trapaidze A, Hureau C, Bal W, et al. “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. 2012. PMID 21898044. pubmed.ncbi.nlm.nih.gov/21898044.
5. National Center for Biotechnology Information. “PubChem Compound Summary for CID 7408502, L-Alanyl-L-histidyl-L-lysine.” pubchem.ncbi.nlm.nih.gov/compound/7408502 (peptide formula, mass, CAS).
6. National Center for Biotechnology Information. “PubChem Compound Summary for CID 168431292, AHK-Cu.” pubchem.ncbi.nlm.nih.gov/compound/168431292 (CAS 682809-81-0; deposited as the monohydrochloride, with the caveat noted above).