Epitalon (Epithalon, AEDG) vs SS-31 (Elamipretide)

Epitalon (Epithalon, AEDG)

Epitalon, also spelled epithalon, is the synthetic tetrapeptide Ala-Glu-Asp-Gly, modelled on epithalamin, a peptide extract of bovine pineal gland. It came out of a Russian research programme on short regulatory peptides, and nearly all of the published work comes from that programme and its collaborators. The studies include cultured human cells, rodents and fruit flies, together with some human studies reported mostly in Russian-language journals. The topics are ageing biology, telomere maintenance and pineal function. Independent replication outside that group is limited, and the human data are sparse and come almost entirely from the same source.

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 Epitalon (Epithalon, AEDG) acts

No receptor for Epitalon has been identified, and most mechanistic proposals come from the same research school. Cell-culture studies from that group have reported induction of telomerase activity and telomere elongation in human somatic cells, which normally express little telomerase. Other papers propose that short peptides of this kind enter the nucleus and bind DNA or histones, altering the expression of particular genes; this idea has not been widely tested elsewhere. Animal studies have examined melatonin secretion by the pineal gland and circadian markers. The overall picture rests on a narrow base of laboratories.

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: Epitalon (Epithalon, AEDG), Tetrapeptide; SS-31 (Elamipretide), Aromatic-cationic tetrapeptide — mitochondria-targeted
• Length: Epitalon (Epithalon, AEDG), 4 amino acids; SS-31 (Elamipretide), 4 amino acids
• Molecular weight: Epitalon (Epithalon, AEDG), 390.35 g/mol; SS-31 (Elamipretide), 639.8 g/mol
• Molecular formula: Epitalon (Epithalon, AEDG), C14H22N4O9; 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.