SS-31

SS-31 is a synthetic tetrapeptide, meaning four amino acid residues, that concentrates in the inner mitochondrial membrane and associates with the phospholipid cardiolipin. Its sequence is D-Arg-Dmt-Lys-Phe-NH2, its formula C32H49N9O5, and its free-base weight 639.8 g/mol. Two residues fall outside the twenty genetically encoded L-amino acids: the arginine is the D-enantiomer, and Dmt, 2′,6′-dimethyltyrosine, is wholly synthetic. The C-terminus is an amide rather than a free acid. That composition is deliberate: it keeps the molecule a genuine peptide by chemistry while placing it outside the substrate range of much proteolytic machinery.

The molecule carries a net positive charge at physiological pH and is amphipathic, meaning it has both water-attracting and lipid-attracting regions. Published work attributes its mitochondrial localisation to that combination rather than to a receptor. Cardiolipin, its binding partner, is a four-chain phospholipid found almost exclusively in the inner mitochondrial membrane, where it makes up roughly 15 to 20 percent of phospholipid content and shapes cristae curvature and respiratory complex assembly. SS-31 is used in the literature as a membrane-directed probe of mitochondrial bioenergetics; material listed here is reference chemical for laboratory research.

SS-31 emerged from a series of cell-permeable, mitochondria-targeted peptides developed by Hazel Szeto and Peter Schiller, first reported in 2004 (PubMed 15178689). It later carried the codes MTP-131 and Bendavia.

Birk and colleagues reported that SS-31 binds cardiolipin and restored respiration in ischemic mitochondria, which reframed it from a general antioxidant to a cardiolipin-directed agent (PubMed 23813215). Russo and colleagues examined SS-31 in tafazzin knockdown mice, a model of defective cardiolipin remodelling (PubMed 36400945).

The evidence base is unusually developed for a compound in this catalogue. Preclinical findings across cardiac, renal and neuronal models are broadly concordant, while human trials varied by indication and endpoint, several missing their primary endpoints (PubMed 37268435). Research-grade material listed here is not the approved prescription formulation of elamipretide.

The mechanism described in the literature is a lipid interaction, not receptor binding. SS-31 is reported to accumulate in the inner mitochondrial membrane and associate with cardiolipin through electrostatic and hydrophobic contacts, altering the electrostatic surface potential of cardiolipin-rich domains (PubMed 23813215). Reported downstream observations include preserved cristae architecture and more stable respiratory supercomplexes (PubMed 40294492).

A distinction helps here. MOTS-c is encoded in mitochondrial DNA and acts as a signalling peptide; SS-31 is fully synthetic and has no identified receptor. It also runs opposite to an uncoupler such as BAM15, which dissipates the proton gradient SS-31 is described as helping preserve.

The methodology caveat is that cardiolipin content and acyl composition vary by tissue, age and model, so an effect in cardiac mitochondria may not transfer elsewhere. Exposure conditions are defined in each cited study’s methodology.

SS-31 vial material is stored at -20°C, shielded from light, and kept sealed until use. Freeze-thaw cycling is avoided. No stability duration is asserted here; lot data appear on the Certificate of Analysis.

Peptides carrying a free phenol and a guanidine group are handled as light-sensitive, moisture-sensitive solids. Conditions for material already in solution belong to the study protocol.

Reconstitution means returning a lyophilized (freeze-dried) compound to solution. No reconstitution procedure appears on this page. Solvent, quantity and technique belong to the methodology of the study reproduced.

As a general solubility class, SS-31 is a small cationic peptide with useful aqueous solubility, unlike lipophilic small molecules that need an organic co-solvent. Solid peptide is hygroscopic, meaning it takes up atmospheric moisture. The lot COA records appearance and identity.

Identity for SS-31 is confirmed from documentation rather than assumed. Verified purity is documented per lot on the Certificate of Analysis, with identity established by chromatographic and mass spectrometric methods. Check that the COA sequence shows D-arginine and dimethyltyrosine, because an all-L variant is a different molecule.

Both SS-31 listings come from supplier brands rather than the house brands, and each carries its manufacturer’s documentation. Closely related truncations are the realistic impurity class, so the COA chromatographic trace is the practical check.

Compounds researchers commonly study alongside SS-31:

• MOTS-c.
  A mitochondrial-derived signalling peptide studied in overlapping bioenergetic pathways.
• BAM15.
  A small-molecule mitochondrial uncoupler, not a peptide, acting on the same organelle in the opposite direction.
• 5-Amino-1MQ.
  A small-molecule NNMT inhibitor, not a peptide, studied in NAD+ related metabolism.
• SLU-PP-332 (entry forthcoming).
  A small-molecule ERR agonist, not a peptide, studied in oxidative metabolism.

Zhao K, Zhao GM, Wu D, et al. (2004). Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. Journal of Biological Chemistry.
PubMed 15178689

Birk AV, Liu S, Soong Y, et al. (2013). The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology.
PubMed 23813215

Russo S, De Rasmo D, Signorile A, et al. (2022). Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice. Scientific Reports.
PubMed 36400945

Karaa A, Bertini E, Carelli V, et al. (2023). Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology.
PubMed 37268435

Sabbah HN, Alder NN, Sparagna GC, et al. (2025). Contemporary insights into elamipretide’s mitochondrial mechanism of action and therapeutic effects. Biomedicine and Pharmacotherapy.
PubMed 40294492

Peptides.com lists two SS-31 research products from two brands, both in vial format. Real Peptides SS-31 is specified at 10mg and 50mg per vial, and Groov Bioscience SS-31 at 10mg, 50mg and 100mg per vial. Those are product specifications rather than research quantities. Each lot has a published Certificate of Analysis, available through Lab Reports.

• Browse all SS-31 research products
• Real Peptides SS-31, 10mg and 50mg vial
• Groov Bioscience SS-31, 10mg, 50mg and 100mg vial
• Collections: Research Vials. Documentation: COA and Lab Testing.

These products are sold for Research Use Only and are not intended for human consumption.