# SS-31 (Elamipretide): Cardiolipin Targeting, Mechanism and Laboratory Use > A four-residue engineered peptide that reaches the inner mitochondrial membrane by charge and chemistry rather than by any receptor, and what it does there. Web page: https://peptidemedixeu.com/en/learn/what-is-ss-31/ · Peptide Medix EU · 6 min read · Updated: 2026-04-27 SS-31 is an engineered tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2, built to collect at the inner mitochondrial membrane and bind cardiolipin, the phospholipid unique to that membrane. It is nothing like the mitochondrially encoded peptides: no gene codes for it. It belongs to the Szeto-Schiller aromatic-cationic family, and what defines it is targeting rather than receptor activation. Listed variously as [elamipretide](https://peptidemedixeu.com/en/products/ss-31/), MTP-131 and Bendavia, it is the most clinically developed compound on our mitochondrial shelf, supported by a registrational trial programme. Peptide Medix EU supplies SS-31 (Elamipretide) as lyophilized powder in 10 mg, 30 mg and 50 mg vials within the mitochondrial peptides range. ## Defining SS-31 SS-31 is a four-residue peptide alternating cationic and aromatic amino acids: D-arginine, 2',6'-dimethyl-L-tyrosine (Dmt), lysine and phenylalanine, closed with a C-terminal amide. Its identifiers are CAS 736992-21-5, formula C32H49N9O5 and molar mass 639.80 g/mol. Each structural feature serves a purpose. D-arginine in position 1 blocks aminopeptidase attack, and C-terminal amidation eliminates the free carboxylate that carboxypeptidases would otherwise recognise. Its net +3 charge drives accumulation in the matrix space, while the pair of aromatic side chains supply enough [lipophilicity](https://peptidemedixeu.com/en/glossary/lipophilic/) for partitioning into a membrane. Dmt is not a proteinogenic amino acid but a synthetic tyrosine derivative that increases aromaticity and metabolic stability. The upshot is a peptide that concentrates in mitochondria through physicochemistry alone, needing neither a receptor nor an import signal. ## Where the molecule came from Hazel Szeto and Peter Schiller developed the series in the early 2000s from an unrelated starting point: Dmt-containing opioid peptide analogues. The group observed that certain cationic-aromatic sequences built up in mitochondria at several thousand times their extracellular concentration. Subsequent members of the series, including SS-31, were designed to retain that mitochondrial targeting while shedding opioid receptor activity, and SS-31 is reported to lack meaningful opioid activity at the concentrations used in mitochondrial studies. One difference from earlier targeting approaches is important: SS-31 uptake does not rely on membrane potential. Triphenylphosphonium conjugates accumulate because the matrix carries a negative charge, so they fail precisely in the depolarised, dysfunctional mitochondria they are supposed to reach. SS-31 accumulates regardless of potential, which is the practical case for using it in models of mitochondrial dysfunction. ## Proposed mechanism Across the literature the mechanism revolves around cardiolipin, a four-tailed phospholipid found almost only in the inner mitochondrial membrane, where it shapes the cristae and holds respiratory complexes together in supercomplexes. SS-31 binds cardiolipin through a mix of electrostatic and hydrophobic interactions. Two downstream effects are described. Cardiolipin normally tethers cytochrome c to the membrane; if that association changes, cytochrome c acquires peroxidase activity, oxidises cardiolipin and sets off the release cascade leading to apoptosis. SS-31 binding is reported to keep the cytochrome c-cardiolipin pairing in its electron-carrier state and to damp the peroxidase behaviour. Separately, cristae shape and supercomplex organisation are reported to recover in models where they had become disordered, alongside better respiratory efficiency and less electron leak into reactive oxygen species. For study design, the key point is that SS-31 is no antioxidant in the scavenging sense. Its reported effect is structural, restoring an organisational property of the membrane so that fewer reactive species arise in the first place, rather than mopping them up afterwards. It also has no identified receptor, because none is required. ## Research to date ### Ischaemia-reperfusion and cardiac studies The biggest preclinical body of work involves rodent and large-animal models of cardiac ischaemia-reperfusion injury, where smaller infarcts and preserved mitochondrial respiration have been reported. A parallel literature exists for renal ischaemia-reperfusion. ### Primary mitochondrial myopathy The clinical programme focused chiefly on primary mitochondrial myopathy, where a [Phase 3](https://peptidemedixeu.com/en/blog/retatrutide-explained-published-phase-3-data-reported-2026/) trial did not achieve its primary functional endpoint despite promising earlier-phase signals. The result is instructive: a mechanism that performs well in preclinical models did not translate neatly into a functional clinical outcome. ### Barth syndrome Barth syndrome results from mutations in tafazzin, the enzyme that remodels cardiolipin, making it the most mechanistically fitting indication for a cardiolipin-binding molecule. A crossover trial and its open-label extension have been published, and regulatory assessment of elamipretide in this rare disease has shifted over recent years. Whatever the present position, an approved medicine is a different article from research-grade material, and the two must never be equated. ### Eye and age-related models Trials in dry age-related macular degeneration and geographic atrophy looked at retinal pigment epithelium function, an application chosen because that tissue is unusually rich in mitochondria. ### Aging and skeletal muscle Rodent and ex-vivo human muscle studies have measured mitochondrial respiration, ATP output and resistance to fatigue in aged tissue, reporting gains in respiratory parameters. This remains preclinical work. ## Formats and sizes The three vial sizes span the range from plate-scale in-vitro series to larger preclinical studies. For the comparison with the mitochondrially encoded alternative, see [MOTS-c](https://peptidemedixeu.com/en/learn/what-is-mots-c/) vs SS-31. ## Reconstitution and storage in the lab SS-31 dissolves readily in water and in bacteriostatic water; a short, strongly cationic peptide is about as cooperative as peptides come. Add solvent down the vial wall and swirl rather than shake. The numbers are a lab calculation: a 30 mg vial made up in 3 [mL of diluent](https://peptidemedixeu.com/en/learn/bacteriostatic-water-vs-sterile-water/) gives 10 mg/mL (10,000 mcg/mL), so 0.1 mL, the 10-unit mark on a U-100 syringe, holds 1,000 mcg. At 639.80 g/mol, 1 mg equals roughly 1.56 µmol, a handy conversion because most [published in-vitro](https://peptidemedixeu.com/en/glossary/in-vitro/) work with this compound is reported in molar rather than mass units. Method details are in our reconstitution guide. Keep lyophilized vials sealed at −20 °C away from light and moisture. Store reconstituted material at 2-8 °C for the duration of the study, or aliquot and freeze it for longer projects. Dmt is a phenol and therefore oxidation-sensitive, so protection from light and air matters as much here as for any tyrosine-containing peptide. Broader practice is covered in [how to store](https://peptidemedixeu.com/en/learn/how-to-store-peptides/) peptides. ## Purity and reading the COA Identity is confirmed by a mass spectrometry result matching 639.80 g/mol. For this sequence, stereochemistry is the specification a routine certificate is least able to demonstrate: the arginine must be the D-enantiomer, and mass spectrometry cannot tell D from L. When enantiomeric purity matters to the experiment, chiral HPLC or amino acid analysis is the appropriate method, and seeing it on a certificate is a real quality indicator. The usual entries otherwise apply: purity as main-peak area, counter-ion (reversed-phase purification usually leaves a [TFA salt](https://peptidemedixeu.com/en/glossary/tfa-salt/)), lot number and date of manufacture. Our guide to reading a peptide certificate of analysis works through each section. ## Regulatory position Elamipretide has undergone an extensive clinical programme and regulatory assessment for a rare mitochondrial disorder, a status that has changed over recent years. Two things remain true regardless. The research-grade material supplied here is not a pharmaceutical, has not been made to pharmaceutical standards and is not equivalent to any approved or investigational medicine sharing the same molecular name. There is no approved use for it in any form. ## Related compounds and further reading The genetically encoded members of this field are MOTS-c and Humanin, mitochondrial-derived peptides that work by signalling rather than membrane targeting. Among cofactors, NAD+ addresses redox capacity instead of membrane structure. For broader orientation, read our peptides for energy and mitochondria research overview. ## Frequently asked questions ### What is SS-31 in chemical terms? An engineered tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2, weighing 639.80 g/mol and based on alternating cationic and aromatic residues. Dmt stands for 2',6'-dimethyl-L-tyrosine, a synthetic tyrosine derivative rather than a natural amino acid. The compound also appears as elamipretide, MTP-131 and Bendavia. ### How does SS-31 get into mitochondria without a receptor? Through physicochemistry. Its net +3 charge drives accumulation in the matrix space while two aromatic side chains allow it to partition into membrane. Importantly that uptake does not depend on membrane potential, unlike triphenylphosphonium conjugates, which fail in the very depolarised mitochondria they target. ### What happens when SS-31 binds cardiolipin? Cardiolipin shapes cristae folds and anchors cytochrome c. SS-31 binding reportedly keeps the cytochrome c-cardiolipin association in its electron-carrier state, damping the peroxidase activity that starts apoptotic release, and improves cristae architecture and supercomplex organisation in disordered models. ### Does SS-31 act as an antioxidant? Not by scavenging. The reported action is structural: it restores an organisational feature of the inner membrane so fewer reactive species form, rather than neutralising them once they exist. The distinction matters when choosing readouts and comparator compounds. ### What were the results of the clinical programme? Mixed. A Phase 3 study in primary mitochondrial myopathy missed its primary functional endpoint even though earlier phases had shown signals. Work in Barth syndrome, caused by mutations in the cardiolipin-remodelling enzyme tafazzin and therefore the most mechanistically apt indication, has been through changing regulatory assessment. ### Which specification is hardest to verify on an SS-31 certificate? Stereochemistry. The arginine has to be the D-enantiomer, and mass spectrometry cannot separate D from L. Where enantiomeric purity is important, chiral HPLC or amino acid analysis is the right test, and its appearance on a certificate is a meaningful quality signal beyond the purity percentage. ### How is SS-31 different from MOTS-c and humanin? In both origin and mode of action. MOTS-c and humanin are encoded in mitochondrial DNA and act as signalling peptides on cytosolic and nuclear pathways, whereas SS-31 is an engineered molecule with no gene at all, working by accumulating at the inner membrane and binding a phospholipid. --- For laboratory research use only. 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