AHK-Cu

AHK-Cu (also written AHK Cu) is a synthetic copper peptide: the tripeptide L-alanyl-L-histidyl-L-lysine (Ala-His-Lys) holding one copper(II) ion. It is the alanine analog of GHK-Cu. Alanine replaces the N-terminal glycine, while the copper-anchoring histidine and the C-terminal lysine stay the same (Pyo et al., 2007; Mateescu et al., 2026). Its published record is thin.

A PubMed search in October 2026 found one primary study, which used human hair follicles cultured ex vivo and cultured dermal papilla cells.

PubChem CID 168431292 lists the same formula, weight and CAS number and is the source of the systematic name; the free-peptide data are from CID 7408502.

Published work touching AHK-Cu falls into six areas, and only the first two report AHK-Cu data.

Human hair follicles in organ culture

In the one primary AHK-Cu study, a dermatology group at Seoul National University exposed human hair follicles cultured ex vivo to AHK-Cu at 10⁻¹² to 10⁻⁹ M and reported that it stimulated follicle elongation (Pyo et al., 2007). The authors proposed that papilla cell proliferation and reduced apoptosis may underlie the effect. Model: human hair follicles, ex vivo. These are organ-culture data from one laboratory, and we found no animal or human follow-up in PubMed.

Dermal papilla cells: proliferation and apoptosis markers

Dermal papilla cells are specialized fibroblasts important in follicle formation and growth. In the same study, AHK-Cu at 10⁻¹² to 10⁻⁹ M stimulated proliferation of cultured dermal papilla cells. At 10⁻⁹ M, Annexin V and propidium iodide flow cytometry showed fewer apoptotic cells, a decrease that was not statistically significant, while the Bcl-2/Bax ratio rose and cleaved caspase-3 and PARP fell (Pyo et al., 2007).

A 2026 review of short peptides in hair research lists this as experimental, ex vivo evidence whose signaling is less well characterized than that of GHK-Cu (Fan et al., 2026). Model: cultured dermal papilla cells.

Fibroblast and extracellular matrix work

We found no PubMed study that measured collagen, glycosaminoglycans or other matrix output in cells exposed to AHK-Cu. The AHK-Cu abstract opens with background describing the tripeptide-copper complex as stimulating dermal fibroblast proliferation and VEGF production and lowering TGF-β1 secretion, but the AHK-Cu endpoints it reports are follicle elongation, papilla cell proliferation and apoptosis markers (Pyo et al., 2007).

The matrix data usually attached to copper peptides come from GHK-Cu, which stimulated collagen synthesis in fibroblast cultures starting between 10⁻¹² and 10⁻¹¹ M and peaking at 10⁻⁹ M, independent of cell number (Maquart et al., 1988). Model: fibroblast culture with GHK-Cu.

AHK without copper: a vitamin C conjugate

The only other PubMed paper built on the AHK sequence tested a vitamin C-linker conjugate of the tripeptide (Vit C-AHK); the abstract mentions no copper. The authors note that vitamin C-conjugated tripeptides were first developed for collagen synthesis and dermal fibroblast growth products. In mouse C2C12 myoblasts stimulated with BMP-2, Vit C-AHK raised proliferation, alkaline phosphatase induction, Smad1/5/8, ERK1/2 and p38 phosphorylation, and mRNA for ALP, BMP-2, osteocalcin and Runx2, without significant cytotoxicity (Jung et al., 2018). Model: mouse C2C12 cell culture only.

Copper binding and the role of the first residue

Peptides that begin NH₂-Xxx-His, as GHK does, hold Cu(II) with three peptide nitrogens plus an outside ligand (the 3N form). Those that begin NH₂-Xxx-Zzz-His, such as Asp-Ala-His-Lys (DAHK) from the N-terminus of human serum albumin, use four peptide nitrogens (the 4N form). A 2017 spectroscopic study of Ala-His-His, which carries both motifs, set out these forms and found a pH-dependent switch between them (Gonzalez et al., 2017).

Without DAHK's aspartate, AHK has its histidine at position 2, which places it in the GHK-type group by sequence alone; we found no structure or binding constant for Cu(II)-AHK in PubMed. A study of GHK and two histidine-replaced analogs concluded that copper complex formation driven by the first residue, and the free lysine side chain, mattered for growth-factor activity in cell culture (Conato et al., 2001). AHK-Cu changes that residue, and no paper has tested the effect. Models: solution chemistry and cell growth assays with related peptides.

How the evidence compares with GHK-Cu

GHK was isolated from human plasma, where it co-purified with roughly equimolar copper. It formed Cu(II) complexes and raised copper uptake into cultured hepatoma cells, and structure-function tests found several tripeptides with a histidyl-lysyl linkage, unnamed in the abstract, nearly as active as GHK on those cells (Pickart et al., 1980).

A PubMed search for GHK and GHK-Cu returns more than 250 records, against one primary study for AHK-Cu. A 2026 evidence-mapping review of GHK-Cu lists AHK-Cu as a synthetic relative with histidine-anchored copper binding and judges its evidence base small and poorly characterized; it also finds clinical evidence for GHK-Cu itself sparse (Mateescu et al., 2026). Models: hepatoma cell culture and a structured literature review.