GHK-Cu

GHK-Cu (Glycine-Histidine-Lysine copper(II) complex) is a naturally occurring tripeptide-copper complex found in human plasma, saliva, and urine, present at approximately 200 ng/mL in young adults and declining to approximately 80 ng/mL with age — a published decline that has positioned GHK-Cu within longevity and tissue maintenance research programmes. The compound's remarkably broad published biological activity profile spans fibroblast collagen synthesis, MMP regulation, angiogenesis, antioxidant defence, gene expression regulation, and hair follicle biology, making it one of the most multi-dimensional naturally occurring peptide-metal complexes in the research literature.

The copper coordination chemistry follows the ATCUN (Amino Terminal Copper and Nickel) binding motif, which requires a free N-terminal amino group at position 1, any amino acid at position 2, and histidine at position 3. GHK (Gly-His-Lys) perfectly satisfies this motif: the N-terminal glycine amine, the deprotonated amide nitrogen between positions 1 and 2, and the N3 imidazole nitrogen of His2 provide three of the four square planar coordination sites, with a water molecule occupying the fourth. This square planar Cu(II) coordination is responsible for the compound's characteristic blue-green colour — Cu(II) d-d electronic transitions absorb at approximately 600-700 nm (red-orange), and the reflected/transmitted complementary colour appears blue-green. The colour intensity and hue serve as a practical quality indicator: correctly coordinated GHK-Cu appears a consistent medium blue-green; pale, colourless, or dark brown solutions indicate copper loss or reduction.

The femtomolar dissociation constant (Kd approximately 10^-15 M) makes GHK-Cu thermodynamically one of the most stable copper-peptide complexes in biology, comparable to cuproenzyme copper-binding sites. Under physiological conditions, the copper is sequestered within the complex and is bioavailable only through the intact GHK-Cu molecule's interaction with cellular copper transport systems — not as free ionic copper.

The foundational collagen synthesis research by Pickart in the 1970s-80s established that GHK-Cu stimulates collagen type I, III, and IV synthesis in fibroblast cultures, alongside elastin and glycosaminoglycan production. More recent transcriptomic research by Pickart and Margolina (IJMS, 2018) using microarray analysis of human fibroblasts treated with 1-10 nM GHK-Cu identified several thousand differentially expressed genes — a breadth of transcriptional response that has led to proposals of a global gene expression reset effect. Upregulated categories included antioxidant defence (SOD1, GPX1, CAT), anti-inflammatory pathways (IL-10, SOCS3), DNA repair genes, and proteasome components. Downregulated categories included inflammatory mediators and cancer-associated pathways.

MMP/TIMP balance regulation by GHK-Cu has been examined in fibroblast models, with published data suggesting GHK-Cu suppresses excessive MMP activity (particularly MMP-1 and MMP-2) while maintaining physiological matrix remodelling capacity — mediated through SP1 transcription factor activation driving TIMP expression. This MMP regulatory activity is relevant for wound healing, ECM remodelling, and skin biology research.

Hair follicle research connects GHK-Cu to dermal papilla cell biology: copper is an essential cofactor for lysyl oxidase, which cross-links collagen and elastin in the dermal papilla ECM, maintaining follicle structural integrity through multiple growth cycles.

MW: 403.45 g/mol. CAS: 89030-95-5. Molecular formula: C14H23CuN6O4+. Avoid reducing agents (DTT, BME, TCEP). Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C, protected from light. For laboratory and analytical research purposes only.