Pal-AHK peptide is primarily studied for its potential interactions with dermal papilla cells (DPCs) that are posited to act as the primary regulatory cells of the hair follicle. The peptide may do so by interacting with various growth factors regulating cellular proliferation, apoptosis, and vascularization.
Pal-AHK Structure
In silico analysis by Kecel-Gunduza et al. suggests that the AHK sequence may have a high affinity to copper ions, which may be primarily driven by the histidine residue, whose imidazole side chain acts as the primary anchoring point for Cu²⁺ ions through coordination chemistry.(2) Lysine’s amino group may also provide additional binding stabilization, while alanine contributes structural flexibility.
These residues are posited to remain fully intact even after palmitoylation, as the process appends the C16 fatty acid chain to the N-terminus of the peptide, specifically the alanine residue, leaving the histidine coordination site undisturbed. The palmitoylation process is further posited to support the potential of the peptide to penetrate through lipophilic structures such as dermal cell cultures and similar laboratory models.
Pal-AHK Mechanisms and Cellular Apoptosis
Sadgrove et al. suggests that the main mechanisms behind the peptide’s interactions with the regulatory cells of the mammalian hair follicle may include a “reduced expression of TGF‐β1 and increased hair shaft elongation, increased expression of vascular endothelial growth factor and reduced negative growth factors.”(3) Furthermore, these researchers cite a paper by Pyo et al. which suggests that when these follicular epithelial cells are exposed to the peptide, the latter may promote proliferation and differentiation.
Binding Pal-AHK to copper ions may further support this potential.(4) The paper suggests that the peptide may have anti-apoptotic action on dermal papilla cells, reducing apoptosis by approximately 3.48%. This modest reduction in apoptotic cells was further supported at the protein level, where the peptide appeared to shift the balance between pro- and anti-apoptotic regulators within the Bcl-2 family, suggesting the action may be mechanistically reproducible even if not yet statistically robust at the cell-count level.
Given that Bcl-2 expression is reported to be dominant during telogen-to-anagen transition, this shift may be mechanistically relevant to hair cells’ cycle re-entry. Consistent with the Bcl-2/Bax shift, another central executioner protease in apoptotic cascades called Caspase-3 may also respond to Pal-AHK, especially when the latter binds to copper ions. Pyo et al. suggest that the peptide may decrease the active form of caspase-3 by approximately 42.7% and one of its primary downstream cleavage targets, called PARP, by approximately 77.5%, while procaspase-3 levels apparently remained unchanged.
The study also hypothesized that due to the structural similarities between the AHK and GHK sequences, Pal-AHK may also interact with growth factors, such as upregulating vascular endothelial growth factor (VEGF) and downregulating TGF-β1. VEGF may support perifollicular vascularity and support follicle size, while androgen-inducible TGF-β1 derived from DPCs has been implicated in suppressing epithelial cell proliferation.
Pal-AHK Mechanisms and Collagen Synthesis
Laboratory research by Patt et al. suggests that the peptide potentially “increases the growth and viability of dermal fibroblasts while stimulating the production of collagen” when bound to copper ions.(5) Dermal fibroblasts are posited to be the principal cellular source of collagen and other extracellular matrix proteins, so these proliferative and viability-supporting properties may be upstream prerequisites for downstream matrix remodeling activity.
In the same fibroblast culture model, the peptide also appeared to stimulate collagen type I secretion by approximately 300% when compared to placebo. This suggests Pal-AHK may act not merely as a mitogen but as an inducer of the collagen biosynthesis pathway in fibroblasts.
Beyond collagen, the copper affinity of peptide sequence may contribute to matrix remodeling through its role as a cofactor for lysyl oxidase, the enzyme posited to crosslink elastin and collagen. The research cited also posits that copper peptides may activate matrix metalloproteases (MMPs) and promote angiogenesis, potentially via upregulation of VEGF.
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References:
- Kapoor R, Shome D, Vadera S, Kumar V, Ram MS. QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal Efficacy Study. Plast Reconstr Surg Glob Open. 2020 Aug 25;8(8):e2843. doi: 10.1097/GOX.0000000000002843. PMID: 32983753; PMCID: PMC7489598.
- Kecel-Gunduza S, Kocb E, Bicaka B, Kokcub Y, Ozela AE, Akyuzc S. IN SILICO ANALYSIS FOR CHARACTERIZING THE STRUCTURE AND BINDING PROPERTIES OF ALA-HIS-LYS (AHK) TRIPEPTIDE. The Online Journal of Science and Technology-July. 2020;10(3).
- Sadgrove, N. J., & Simmonds, M. S. J. (2021). Topical and nutricosmetic products for healthy hair and dermal antiaging using “dual-acting” (2 for 1) plant-based peptides, hormones, and cannabinoids. FASEB bioAdvances, 3(8), 601–610. https://doi.org/10.1096/fba.2021-00022
- Pyo HK, Yoo HG, Won CH, Lee SH, Kang YJ, Eun HC, Cho KH, Kim KH. The effect of the tripeptide-copper complex on human hair growth in vitro. Arch Pharm Res. 2007 Jul;30(7):834-9. doi: 10.1007/BF02978833. PMID: 17703734.
- Patt, L. M., & Procyte, A. (2009). Neova® DNA Repair Factor Nourishing Lotion Stimulates Collagen and Speeds Natural Repair Process. skin, 1, 2