SS-31 is a synthetic four-residue peptide, D-Arg-Dmt-Lys-Phe-NH2, designed to accumulate at the inner mitochondrial membrane and bind cardiolipin — the signature phospholipid of that membrane. Unlike the mitochondrial-derived peptides, it is not encoded anywhere in the genome; it is an engineered molecule from the Szeto–Schiller aromatic-cationic series, and its defining property is targeting rather than receptor agonism. Also catalogued as elamipretide, MTP-131 and Bendavia, it is the most clinically advanced molecule on this catalogue's mitochondrial shelf, with a registrational trial programme behind it.
MyPeptide supplies SS-31 (Elamipretide) as a lyophilized powder in 10 mg, 30 mg and 50 mg vials within the mitochondrial peptides range. Research use only; not for human or veterinary use.
What is SS-31?
SS-31 is a tetrapeptide with an alternating cationic–aromatic residue pattern: D-arginine, 2',6'-dimethyl-L-tyrosine (Dmt), lysine and phenylalanine, terminating in a C-terminal amide. Its identifiers are CAS 736992-21-5, molecular formula C32H49N9O5 and molecular weight 639.80 g/mol.
Every structural element does a job. The D-arginine at position 1 resists aminopeptidase cleavage; the C-terminal amide removes the free carboxylate and the carboxypeptidase substrate along with it. The net +3 charge drives accumulation in the mitochondrial matrix space, while the two aromatic side chains give the molecule enough lipophilic character to partition into a membrane. The Dmt residue is not a proteinogenic amino acid at all — it is a synthetic tyrosine derivative that raises aromaticity and metabolic stability. The result is a peptide that concentrates in mitochondria by physical chemistry rather than by receptor binding or an import sequence.
Origin and structure
The Szeto–Schiller series came out of work by Hazel Szeto and Peter Schiller in the early 2000s. The starting point was unrelated: opioid peptide analogues built around Dmt, from which the group noticed that certain cationic–aromatic sequences concentrated in mitochondria several thousand-fold over their extracellular concentration. Later members of the series, SS-31 among them, were designed to keep the mitochondrial targeting while dropping opioid receptor activity, and SS-31 is reported to be free of meaningful opioid activity at the concentrations used in mitochondrial work.
An important distinction from earlier mitochondrial-targeting strategies: SS-31's uptake does not depend on membrane potential. Triphenylphosphonium-conjugated compounds accumulate because the matrix is electrically negative, which means they fail in exactly the depolarised, dysfunctional mitochondria they are meant to reach. SS-31's accumulation is potential-independent, which is the practical argument for using it in models of mitochondrial dysfunction.
How SS-31 is thought to work
The mechanism reported across the literature centres on cardiolipin, a four-tailed phospholipid found almost exclusively in the inner mitochondrial membrane, where it organises the cristae folds and holds respiratory chain complexes in supercomplex arrangements. SS-31 binds cardiolipin through combined electrostatic and hydrophobic interaction.
Two downstream consequences are reported. First, cardiolipin normally anchors cytochrome c to the membrane; when that interaction shifts, cytochrome c gains peroxidase activity, oxidises cardiolipin and initiates the release cascade that leads to apoptosis. SS-31 binding is reported to stabilise the cytochrome c–cardiolipin association in its electron-carrier configuration and to suppress the peroxidase behaviour. Second, cristae architecture and supercomplex organisation are reported to improve in models where they were disordered, with associated changes in respiratory efficiency and reduced electron leak to reactive oxygen species.
The framing that matters for study design is that SS-31 is not an antioxidant in the scavenging sense. Its reported action is structural — restoring an organisational feature of a membrane so that fewer reactive species are produced — rather than neutralising species after the fact. It also has no identified receptor, because it does not need one.
What the research has examined
Ischaemia–reperfusion and cardiac models
The largest preclinical literature covers rodent and large-animal models of cardiac ischaemia and reperfusion injury, reporting reductions in infarct size and preservation of mitochondrial respiration. Renal ischaemia–reperfusion models show a parallel body of work.
Primary mitochondrial myopathy
The clinical programme's central effort was in primary mitochondrial myopathy, where a Phase 3 trial reported that the study did not meet its primary functional endpoint, despite earlier-phase signals. This is an instructive result: a mechanism that performs well preclinically did not translate cleanly to a functional clinical outcome.
Barth syndrome
Barth syndrome is caused by mutations in tafazzin, the enzyme that remodels cardiolipin, which makes it the most mechanistically direct indication for a cardiolipin-binding molecule. A crossover trial and its open-label extension have been reported, and regulatory review of elamipretide for this rare condition has been an evolving matter over recent years. Whatever its current status, an approved medicine is not the same substance as research-grade material and the two should never be conflated.
Ophthalmic and age-related models
Trials in dry age-related macular degeneration and geographic atrophy examined retinal pigment epithelium function, an application motivated by the high mitochondrial density of that tissue.
Ageing and skeletal muscle
Rodent and ex-vivo human muscle studies have examined mitochondrial respiration, ATP production and fatigue resistance in aged tissue, reporting improvements in respiratory measures. This is preclinical work.
Forms and sizes we supply
| Attribute | Specification |
|---|---|
| Product | SS-31 (Elamipretide) |
| Also known as | Elamipretide, MTP-131, Bendavia |
| Form | Lyophilized powder, sealed glass vial |
| Available sizes | 10 mg, 30 mg, 50 mg |
| Purity | ≥99% by HPLC, lot-matched COA |
| CAS number | 736992-21-5 |
| Molecular formula | C32H49N9O5 |
| Molecular weight | 639.80 g/mol |
| Sequence | D-Arg-Dmt-Lys-Phe-NH2 (Dmt = 2',6'-dimethyl-L-tyrosine) |
| Molecular target | Cardiolipin, inner mitochondrial membrane |
| Intended use | Laboratory research only |
Three sizes cover the gap between plate-scale in-vitro series and larger preclinical work. The comparison with the mitochondrially encoded alternative is set out in MOTS-c vs SS-31.
Reconstitution and storage in a lab context
SS-31 is freely soluble in water and in bacteriostatic water — a short, strongly cationic peptide is about as easy to dissolve as peptides get. Solvent is added down the vial wall and the vial swirled rather than shaken.
The arithmetic is a laboratory calculation: a 30 mg vial made up with 3 mL of diluent gives 10 mg/mL, or 10,000 mcg/mL, so 0.1 mL — the 10-unit mark on a U-100 syringe — contains 1,000 mcg. At 639.80 g/mol, 1 mg is approximately 1.56 µmol, which is a useful figure because most published in-vitro work with this molecule is expressed in molar rather than mass terms. Method detail is in our reconstitution guide.
Lyophilized vials are held at −20 °C, sealed and protected from light and moisture. Reconstituted material is kept at 2–8 °C within the study window, or aliquoted and frozen for longer work. The Dmt residue is a phenol and is oxidation-sensitive, so protection from light and air matters here as it does for tyrosine-containing peptides generally. Wider practice is in how to store peptides.
Purity, COA and how to read it
Identity confirmation is a mass spectrometry result matching 639.80 g/mol. For this sequence the stereochemistry is the specification that a routine certificate is least likely to prove: the arginine must be the D-enantiomer, and a mass spectrum cannot distinguish D from L. Where enantiomeric purity matters to the experiment, chiral HPLC or amino acid analysis is the relevant test, and its presence on a certificate is a genuine quality signal. Beyond that, the usual entries apply — purity as main-peak area, counter-ion (reversed-phase purification normally leaves a TFA salt), lot number and manufacture date. Our guide to reading a peptide certificate of analysis covers each section.
Regulatory status
Elamipretide has been the subject of a substantial clinical programme and of regulatory review for a rare mitochondrial condition, and that status has evolved over recent years. Two points hold regardless. Research-grade material supplied here is not a pharmaceutical product, has not been manufactured to pharmaceutical standards and is not equivalent to any approved or investigational medicine bearing the same molecular name. It is supplied as a research-use-only chemical for laboratory investigation by qualified personnel — not a supplement, not a medicine, and not for human or veterinary administration.
Related peptides and further reading
The genomically encoded members of this space are MOTS-c and Humanin, both mitochondrial-derived peptides that act by signalling rather than by membrane targeting. On the cofactor side, NAD+ addresses redox capacity rather than membrane structure. Broader orientation is in our peptides for energy and mitochondria research overview.