AHK-Cu vs GHK-Cu: Two Copper-Binding Tripeptides Compared

AHK-Cu and GHK-Cu are both copper(II)-binding tripeptide complexes: GHK-Cu carries the sequence Gly-His-Lys, AHK-Cu carries Ala-His-Lys, and the single glycine-to-alanine swap adds one methyl group (14.03 Da) beside the copper-binding N-terminus. This guide compares the two as laboratory chemistry for researchers choosing a copper-peptide reference material; GHK-Cu is the form in the Happy Peptides catalog.

What is the AHK peptide, and how does it differ from GHK?

The AHK peptide is L-alanyl-L-histidyl-L-lysine (C15H26N6O4, 354.41 g/mol, CAS 126828-32-8, PubChem CID 7408502). GHK is glycyl-L-histidyl-L-lysine (C14H24N6O4, 340.38 g/mol, CAS 49557-75-7, CID 73587). Positions 2 and 3 are identical, histidine then lysine. Only position 1 differs: glycine has no side chain and no stereocentre, while L-alanine carries a methyl side chain and a defined chiral centre.

How does copper coordination differ between AHK-Cu and GHK-Cu?

In GHK-Cu, copper(II) is reported to be held by the N-terminal amino group, the deprotonated backbone amide nitrogen of the first peptide bond and the histidine imidazole nitrogen, with a further position filled by a carboxylate oxygen or solvent depending on pH and concentration. AHK places histidine in the same second position behind a free N-terminal amine, so it is expected to bind copper in the same general way. The alanine methyl group adds steric bulk and a chiral centre next to that site, which could shift the apparent stability, the balance of 1:1 and 2:1 species and the visible spectrum. Direct head-to-head data are limited, so regard these differences as something to measure in your own buffer rather than assume. The full GHK-Cu coordination picture is covered in GHK-Cu and copper coordination chemistry in vitro.

How are the two compared in vitro?

• UV-Vis titration: follow the visible d-d band as copper(II) is added to each peptide to map binding stoichiometry and compare band position.
• Competition binding: challenge each complex with a competing ligand such as free histidine or EDTA and compare how readily copper is displaced.
• Isothermal titration calorimetry: estimate apparent affinity at fixed pH, noting that buffers such as phosphate and Tris interact with copper themselves.
• Cell-free redox assays: compare copper(II)/copper(I) cycling with ascorbate and a fluorescent probe, with copper chloride and free peptide as controls.
• Cell-culture models: run matched-molarity comparisons in fibroblast cultures, as described in collagen and fibroblast assays in copper-peptide research.

Compare at equal micromolar concentration rather than equal mg/mL: the two complexes differ in mass by roughly 3.5%, which would otherwise skew the comparison.

Is AHK-Cu available as a research material here?

Happy Peptides does not list an AHK-Cu product, and this page is a chemistry comparison only. If you source AHK-Cu elsewhere, verify identity carefully: PubChem lists an AHK-Cu entry as a monohydrochloride (CAS 682809-81-0), so formula and mass can differ by salt form between suppliers. Ask for a mass-spectrometry result and formula on the certificate; see mass spectrometry for peptide identity confirmation for what to look for.

Related research guides

• GHK vs GHK-Cu: the free tripeptide and its copper complex
• GHK-Cu name variants: one compound
• Sourcing GHK-Cu as a research material: COA, copper content and purity
• A researcher's guide to GHK-Cu

Research-use note

All materials discussed are supplied for in vitro laboratory research use only, and are not for human or animal use.