Pinealon (EDR) vs SS-31 (Elamipretide)

Pinealon (EDR)

Pinealon is the synthetic tripeptide Glu-Asp-Arg (EDR), one of the short 'bioregulator' peptides described by a Russian research group. That group proposes that very short peptides can act on gene expression directly, without a conventional receptor, a view that has had little independent testing. Most published work on Pinealon comes from the same group and its collaborators. It consists of experiments in cultured neurons and other cells, rodent studies centred on the nervous system and oxidative stress, and computer modelling of how the peptide might bind DNA. Human data are very limited.

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 Pinealon (EDR) acts

The originating group has proposed that EDR enters cells and their nuclei and binds particular DNA sequences or histone proteins, changing the expression of nearby genes. Support for this comes mainly from molecular modelling and in vitro binding experiments. In cultured neurons and other cells exposed to oxidative stress, Pinealon has been reported to lower the accumulation of reactive oxygen species and to alter ERK1/2 (MAPK) signalling, and rodent studies from the same group have measured markers of oxidative damage in brain tissue. No specific receptor for the peptide has been identified, and independent confirmation of these mechanisms is limited.

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: Pinealon (EDR), Tripeptide; SS-31 (Elamipretide), Aromatic-cationic tetrapeptide — mitochondria-targeted
• Length: Pinealon (EDR), 3 amino acids; SS-31 (Elamipretide), 4 amino acids
• Molecular weight: Pinealon (EDR), 418.40 g/mol; SS-31 (Elamipretide), 639.8 g/mol
• Molecular formula: Pinealon (EDR), C15H26N6O8; 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.