AHK-Cu (Copper Tripeptide-3) vs SS-31 (Elamipretide)

AHK-Cu (Copper Tripeptide-3)

AHK-Cu is a copper(II) complex of the synthetic tripeptide alanyl-histidyl-lysine, a close relative of the naturally occurring GHK-Cu. The two differ only in the first residue: alanine here, glycine in GHK. GHK is found in human plasma and has a long history in the literature as a copper-binding peptide; AHK is a synthetic variant with the histidine in the same position. Published work on AHK-Cu is small and mostly in vitro, using cultured human dermal papilla cells and fibroblasts, and isolated hair follicles kept alive in organ culture. Controlled human studies are scarce, and much of the wider discussion of the compound borrows from GHK-Cu rather than from data on AHK-Cu itself.

SS-31 (Elamipretide)

SS-31, also named elamipretide, is a synthetic tetrapeptide of alternating aromatic and basic residues that concentrates in mitochondria. Its sequence is D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2′,6′-dimethyltyrosine; the N-terminal D-amino acid slows enzymatic breakdown, and the peptide carries a net charge of +3 at neutral pH. The SS prefix refers to Szeto and Schiller, who described a series of related peptides that grew out of opioid peptide research, although SS-31 is reported to have no opioid activity. Most mechanistic work uses isolated mitochondria, cultured cells and rodent ischaemia models. It has also been tested in human clinical trials, chiefly in inherited mitochondrial disorders, and those data are smaller and less consistent than the preclinical literature.

How AHK-Cu (Copper Tripeptide-3) acts

In GHK-Cu, the copper ion is held by the N-terminal amine, the deprotonated amide nitrogen between the first two residues and a nitrogen of the histidine imidazole ring. AHK is thought to bind copper in the same way, since its histidine sits in the same position. Copper-peptide complexes of this kind have been studied as carriers that deliver copper, a cofactor for enzymes such as lysyl oxidase and superoxide dismutase, to cells. In cultured human dermal papilla cells, AHK-Cu has been reported to affect cell proliferation and markers of apoptosis, including the balance of Bcl-2 and Bax. Which receptors or transporters mediate these observations has not been established.

How SS-31 (Elamipretide) acts

SS-31 crosses cell membranes despite its positive charge and has been reported to accumulate at the inner mitochondrial membrane. The favoured explanation is binding to cardiolipin, a phospholipid largely confined to that membrane, through electrostatic and hydrophobic contacts. Biophysical studies suggest this binding changes membrane surface charge and the way cytochrome c associates with cardiolipin, including cytochrome c's peroxidase activity. In isolated mitochondria and cell models, its effects on cristae structure, electron transport and reactive oxygen species have been examined. Early papers described it as a direct antioxidant via its dimethyltyrosine; later work puts more weight on cardiolipin.

The records side by side

• Type: AHK-Cu (Copper Tripeptide-3), Copper tripeptide complex; SS-31 (Elamipretide), Aromatic-cationic tetrapeptide — mitochondria-targeted
• Length: AHK-Cu (Copper Tripeptide-3), 3 amino acids; SS-31 (Elamipretide), 4 amino acids
• Molecular weight: AHK-Cu (Copper Tripeptide-3), 451.39 g/mol; SS-31 (Elamipretide), 639.8 g/mol
• Molecular formula: AHK-Cu (Copper Tripeptide-3), C15H24ClCuN6O4-; SS-31 (Elamipretide), C32H49N9O5

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.