SS-31 Peptide (Elamipretide): a mitochondria-targeted tetrapeptide

SS-31 peptide, also called elamipretide, is a synthetic peptide with four amino acids. It binds cardiolipin in the inner mitochondrial membrane. Laboratory studies examine its effects on mitochondrial structure and energy production. Clinical findings depend on the disease and study. PeptidesDirect supplies SS-31 for laboratory research only, not as a medicine.

Specifications

SequenceD-Arg-Dmt-Lys-Phe-NH2
CAS number736992-21-5
Molecular weight640.8 g/mol
Purity≥98% (HPLC)
TargetCardiolipin, inner mitochondrial membrane

Structure and how SS-31 reaches the mitochondrion

The published SS-31 structure is D-Arg-Dmt-Lys-Phe-NH2. Dmt means dimethyltyrosine. The sequence alternates aromatic and positively charged residues. Zhao et al. (2004) studied this peptide family. The structure allows membrane entry and mitochondrial accumulation without relying on membrane potential. The published sequence describes the research molecule, not a verification of a catalog lot.

Zhao et al. described the Szeto-Schiller series as mitochondria-targeted antioxidants. Their laboratory models showed reduced mitochondrial swelling and oxidative cell death. These were experimental findings, not demonstrated benefits in people.

Cardiolipin binding

Cardiolipin is a lipid in the inner mitochondrial membrane. It helps organise the machinery that produces cellular energy. Birk et al. (2013) studied SS-31 in a kidney injury model involving interrupted blood flow. SS-31 interacted with cardiolipin and helped restore mitochondrial energy production in that model.

Szeto (2014) reviewed SS-31 as a cardiolipin-protective compound. The review emphasised membrane structure as well as oxidative stress. Cristae are folds of the inner mitochondrial membrane. Their structure matters for energy production.

Clinical development as elamipretide

Elamipretide was tested in MMPOWER-3, a randomised placebo-controlled trial in primary mitochondrial myopathy. It did not meet its primary endpoints (Karaa et al., 2023). Positive laboratory findings did not establish success in that clinical trial.

On September 19, 2025, the FDA granted accelerated approval to Forzinity (elamipretide) for Barth syndrome in patients weighing at least 30 kg. Approval was based on improved knee-extensor muscle strength, a measure considered reasonably likely to predict benefit. A confirmatory trial is required. This differs from MMPOWER-3 and does not apply to PeptidesDirect research vials.

SS-31 vs MOTS-c

SS-31 and MOTS-c both appear in mitochondrial research, but they are different molecules. SS-31 acts at the inner mitochondrial membrane. MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA. Lee et al. (2015) studied its metabolic signalling effects in mice. These component studies do not establish an effective combination.

  • SS-31: synthetic, 4 amino acids, binds cardiolipin inside mitochondria.
  • MOTS-c: naturally occurring, 16 amino acids, signals metabolic pathways beyond the mitochondrion.
  • Readouts differ: membrane and bioenergetic measures for SS-31; metabolic and signalling measures for MOTS-c.

Interpreting the evidence in laboratory research

Match the measurements to the research question. Oxygen consumption and ATP production assess aspects of energy metabolism. Imaging can assess cristae structure. Respiratory-chain organisation is another possible measurement. An antioxidant assay alone does not capture every proposed mechanism.

Model choice matters too. Several supportive studies examine acute injury, including interrupted and restored blood flow. Those conditions differ from chronic disease and normal aging. Keep the model, measured outcome and limitations together when comparing findings.

Handling in the lab

Keep lyophilised SS-31 cold, dry and protected from light. Follow documented stability conditions and your laboratory protocol. Record the lot and preparation date. Check assay-specific solvent compatibility rather than assuming one preparation works in every model.

Frequently asked questions

What is SS-31 peptide?

A synthetic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2), also called elamipretide, that binds cardiolipin in the inner mitochondrial membrane.

Is SS-31 the same as elamipretide?

Yes — elamipretide is the name used for SS-31 in clinical development.

How does SS-31 get into mitochondria?

Its alternating aromatic-cationic structure lets it cross membranes and accumulate in the inner mitochondrial membrane without depending on the membrane potential.

What is cardiolipin and why does it matter?

Cardiolipin is a lipid of the inner mitochondrial membrane that helps hold the respiratory chain complexes and cristae structure in place. SS-31 binds it.

Is SS-31 an antioxidant?

It was first described within an antioxidant peptide series, but later work reframes the main proposed mechanism as structural stabilisation of cardiolipin and the cristae.

What did the elamipretide clinical trial show?

In the MMPOWER-3 randomised trial in primary mitochondrial myopathy, elamipretide did not meet its primary endpoints (Karaa et al., 2023).

What does D-Arg mean in the published sequence?

D-Arg identifies the D form of arginine at the start of the published SS-31 sequence. Stereochemistry matters when comparing peptide structures. It should not be inferred from molecular mass alone.

What is the difference between SS-31 and MOTS-c?

SS-31 is a synthetic cardiolipin-binding tetrapeptide; MOTS-c is a naturally mitochondria-encoded 16-amino-acid signalling peptide studied for metabolic effects.

What readouts suit SS-31 research?

Bioenergetic and structural measures — oxygen consumption rate, ATP production, supercomplex integrity and cristae morphology — rather than antioxidant assays alone.

Is SS-31 approved?

The FDA granted accelerated approval to Forzinity (elamipretide) for a specific Barth syndrome indication in September 2025. PeptidesDirect SS-31 is research material, not that approved medicine. It is not for human or veterinary use.

How should SS-31 be stored?

Keep lyophilised SS-31 cold, dry and away from light; refrigerate reconstituted solutions and avoid repeated freeze-thaw cycles.

Where can I buy SS-31 peptide for research?

Compare the listed SS-31 25mg and 50mg options on the product page. These labels describe vial contents, not administration instructions. Review current prices and available lot documents. The research peptides guide research peptides guide explains how to compare suppliers.

Product pages: SS-31 25mg / 50mg · MOTS-c 10mg

Is this product for human use?

No. PeptidesDirect sells this compound for laboratory research only. It is not a drug, food or cosmetic and is not for human or veterinary use. This page summarises published research and is not dosing or medical guidance.

Shop the compounds covered in these FAQs: SS-31 25mg / 50mg · MOTS-c 10mg

References

  1. Zhao K, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem. 2004. PubMed 15178689
  2. Birk AV, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013. PubMed 23813215
  3. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014. PubMed 24117165
  4. Karaa A, et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology. 2023. PubMed 37268435
  5. Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015. PubMed 25738459

Research compounds

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Research Use Only. Not for human or veterinary use. Not dosing or medical guidance.