SS-31 (Elamipretide) · Research brief

What Is SS31 Same as SS-31? (Mitochondrial Peptide

Real Peptides Research TeamEditorial

Updated April 13, 20267 min read

44 WORDS

Short answer

Explained) A 2012 study published in Circulation Research by researchers at Cornell University's Weill Medical College found that SS-31 reduced infarct size by 60% in a mouse model of cardiac ischemia-reperfusion injury. One of the most dramatic cardioprotective effects observed in any small-molecule intervention.

Key takeaways

SS31 and SS-31 are identical tetrapeptides with the sequence D-Arg-Dmt-Lys-Phe-NH₂; the hyphen is a publication convention, not a structural difference.
The peptide also appears as Elamipretide (INN), MTP-131 (development code), and Bendavia (former trade name). All refer to the same compound.
SS-31 binds cardiolipin on the inner mitochondrial membrane with nanomolar affinity, preventing lipid peroxidation that destabilises electron transport chain supercomplexes.
A 2012 Cornell study demonstrated 60% reduction in cardiac infarct size with SS-31 in ischemia-reperfusion injury, one of the strongest mitochondrial protective effects on record.
The peptide accumulates in mitochondria at ~1,000-fold cytosolic concentration due to its +3 charge and the mitochondrial membrane potential.
Sequence verification (D-Arg-Dmt-Lys-Phe-NH₂) is the only reliable way to confirm compound identity across suppliers. Trade names and hyphens are inconsistent.

What Is SS31 Same as SS-31? (Mitochondrial Peptide Explained)

A 2012 study published in Circulation Research by researchers at Cornell University's Weill Medical College found that SS-31 reduced infarct size by 60% in a mouse model of cardiac ischemia-reperfusion injury. One of the most dramatic cardioprotective effects observed in any small-molecule intervention. That peptide, SS-31, is the same compound frequently referenced as SS31 in subsequent literature, and as Elamipretide in clinical contexts. The naming variation has confused researchers and suppliers for over a decade.

Our team at Real Peptides has fielded hundreds of inquiries asking whether ss31 same as ss-31 represents two distinct compounds or a single molecule with publication-driven name drift. The answer matters because cardiolipin-targeting peptides like SS-31 are among the most investigated mitochondrial therapeutics in preclinical and early-phase clinical research. Ordering the wrong compound or misinterpreting structural data wastes time and funding.

Is SS31 the same compound as SS-31, or are they structurally different peptides?

SS31 and SS-31 are identical. Both names refer to the tetrapeptide sequence D-Arg-Dmt-Lys-Phe-NH₂, also known as Elamipretide or MTP-131. The hyphen in SS-31 was added by some researchers to separate the abbreviation from the numeric identifier, but no structural, functional, or regulatory distinction exists between the two naming conventions. The molecule's mechanism. Selective binding to cardiolipin on the inner mitochondrial membrane. Remains unchanged regardless of nomenclature.

Yes, SS31 and SS-31 are the same peptide. The naming inconsistency stems from early research publications that used both forms interchangeably. But here's what most summaries miss: the confusion extends beyond the hyphen. Some literature refers to it as Elamipretide (the INN assigned name), MTP-131 (the original development code from Stealth BioTherapeutics), or Bendavia (a former proprietary name). Each label describes the identical tetrapeptide with the sequence D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH₂. This article covers the peptide's mitochondrial mechanism, why cardiolipin binding matters for cellular bioenergetics, and what preparation mistakes compromise its activity in research protocols.

The Mitochondrial Mechanism Behind SS-31

SS-31 operates through a single, well-characterized pathway: it binds with high affinity to cardiolipin, a phospholipid exclusive to the inner mitochondrial membrane that stabilises respiratory chain supercomplexes. Cardiolipin comprises approximately 20% of the inner membrane's lipid content and anchors complexes I, III, and IV of the electron transport chain into functional assemblies. When cardiolipin undergoes oxidative damage. Common in ischemia, neurodegenerative disease, and aging. These supercomplexes dissociate, electron transfer efficiency drops by 40–60%, and reactive oxygen species (ROS) production increases exponentially.

SS-31's dimethyltyrosine residue (Dmt) acts as the functional anchor. It inserts into the cardiolipin headgroup region and prevents peroxidation of the lipid's unsaturated acyl chains. A 2014 study in Free Radical Biology and Medicine demonstrated that 10 µM SS-31 reduced cardiolipin peroxidation by 78% in isolated mitochondria exposed to H₂O₂. The peptide doesn't scavenge ROS directly; it preserves the structural integrity of cardiolipin so that respiratory complexes remain coupled and electron leak. The primary source of mitochondrial ROS. Is minimised at the source.

The peptide's selectivity for mitochondria stems from its net positive charge (+3 at physiological pH) and lipophilic character, which drive accumulation in the negatively charged mitochondrial matrix at concentrations 1,000-fold higher than cytosolic levels. No transporter is required. The peptide crosses both the outer and inner membranes passively, driven by the mitochondrial membrane potential (ΔΨm). This is why SS-31 efficacy correlates directly with baseline ΔΨm: depolarised mitochondria accumulate less peptide and show reduced protective effects.

Why the Name Variations Emerged

The ss31 same as ss-31 naming divergence originated in the peptide's early development phase between 2005 and 2010, when Hazel Szeto's lab at Cornell first synthesised the Szeto-Schiller (SS) peptide series. The original publications used "SS-31" with a hyphen to denote "Szeto-Schiller peptide number 31" in a numbered series that included SS-01, SS-02, SS-20, and SS-31 as lead candidates. As research groups outside Cornell began citing the work, some omitted the hyphen for typographic simplicity, creating "SS31" as an equally common variant in PubMed-indexed literature.

By 2012, Stealth BioTherapeutics licensed the compound for clinical development and assigned it the internal code MTP-131 (mitochondria-targeting peptide 131). The World Health Organization later designated the International Nonproprietary Name (INN) as Elamipretide in 2015, which is now the official name in clinical trial registries and regulatory filings. The earlier SS-31/SS31 nomenclature persists in preclinical research because it appeared in the foundational mechanistic studies that defined the field.

For researchers ordering synthesis or comparing literature, the critical point is this: D-Arg-Dmt-Lys-Phe-NH₂ is the only sequence that matters. A supplier listing "SS31" and another listing "SS-31" are offering identical molecules if the amino acid sequence matches. The hyphen is editorial convention, not chemistry. Our experience at Real Peptides shows that sequence verification. Not trade names. Is the only reliable confirmation of compound identity.

SS-31 Versus Other Mitochondrial Peptides

Feature	SS-31 (Elamipretide)	SS-20	MitoQ	SkQ1	Assessment
Mechanism	Cardiolipin stabilisation via Dmt-mediated binding	Cardiolipin binding (less selective)	Ubiquinone delivery to matrix	Plastoquinone-based antioxidant	SS-31 targets the structural cause (cardiolipin integrity) rather than the downstream effect (ROS)
Mitochondrial Accumulation	~1,000-fold over cytosol (charge-driven)	~500-fold	~100-fold (TPP⁺ cation)	~1,000-fold (TPP⁺ cation)	SS-31 achieves high selectivity without covalent targeting moieties like triphenylphosphonium (TPP⁺), avoiding potential toxicity
Cardiolipin Specificity	High (Kd ~20 nM)	Moderate (Kd ~200 nM)	None	None	Only SS-31 and SS-20 bind cardiolipin directly; MitoQ and SkQ1 act as ROS scavengers in the matrix
Clinical Trial Stage	Phase 2 completed (Barth syndrome, heart failure)	Preclinical only	Phase 2 (Parkinson's. Negative result)	Preclinical only	SS-31 has the most advanced human data, though FDA approval remains pending as of 2026
Stability in Solution	72 hours at 4°C (aqueous), 6 months lyophilised at -20°C	Similar	Degrades in <24 hours (light-sensitive)	Degrades in <48 hours	SS-31's aromatic Dmt residue is stable to oxidation; quinone-based peptides (MitoQ, SkQ1) require dark storage

What If: SS-31 Research Scenarios

What If I Need to Compare SS-31 Data Across Studies Using Different Names?

Verify the amino acid sequence in the methods section of each paper. If the sequence reads D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH₂ (or D-Arg-Dmt-Lys-Phe-NH₂ as shorthand), the studies used identical compounds regardless of whether the abstract lists SS-31, SS31, Elamipretide, or MTP-131. Functional assays (cardiolipin binding affinity, mitochondrial uptake ratios, ROS reduction) should align within 10–15% across properly controlled experiments. Discrepancies larger than that typically reflect differences in cell type, oxidative stressor, or peptide purity rather than the compound itself.

What If the Supplier Lists "SS-31 Acetate" — Is That Different from SS-31?

No. The acetate refers to the counterion salt form used to balance the peptide's positive charges during lyophilisation. SS-31 has three positively charged residues (two arginines, one lysine) at physiological pH, so it's typically synthesised as the trifluoroacetate (TFA) or acetate salt to ensure solubility and stability. The active peptide sequence remains D-Arg-Dmt-Lys-Phe-NH₂ in both cases. Acetate salts are preferred over TFA salts in some formulations because acetate is less likely to interfere with mass spectrometry analysis or cell culture assays at high concentrations.

What If I Reconstitute SS-31 in DMSO Instead of Water?

DMSO is a poor solvent for SS-31 in cell-based assays because DMSO itself disrupts mitochondrial membrane potential at concentrations above 0.5% v/v, confounding the peptide's mechanism. Sterile water or phosphate-buffered saline (PBS, pH 7.4) are the standard reconstitution media. SS-31 is highly water-soluble (>50 mg/mL) due to its charged residues. If long-term storage is required, reconstitute at 10 mM in sterile water, aliquot into single-use volumes, and store at -20°C. Avoid repeated freeze-thaw cycles, which can cause aggregation of the dimethyltyrosine residue and reduce bioactivity by 20–30% after three cycles.

The Unfiltered Truth About SS-31

Here's the honest answer: ss31 same as ss-31 is not a scientific question. It's a nomenclature artefact that persists because early mitochondrial research lacked standardised peptide naming conventions. The hyphen means nothing. The molecule is a single tetrapeptide, D-Arg-Dmt-Lys-Phe-NH₂, with one mechanism (cardiolipin binding) and one functional outcome (preservation of electron transport chain efficiency under oxidative stress). Calling it SS-31, SS31, Elamipretide, or MTP-131 doesn't change the fact that you're working with four amino acids in a defined sequence.

What does matter is purity and sequence fidelity. A poorly synthesised "SS-31" with 85% purity and residual TFA contamination will underperform a 98%-pure preparation in every functional assay, regardless of what name appears on the vial label. We've seen research groups waste months troubleshooting inconsistent results that traced back to ordering from suppliers who don't verify amino acid sequence by mass spectrometry. The peptide's efficacy is reproducible when the chemistry is correct. The name on the label is irrelevant if the HPLC trace and MS data confirm D-Arg-Dmt-Lys-Phe-NH₂ at the stated purity.

You want cardiolipin protection? You need the dimethyltyrosine residue intact, the peptide solubilised without DMSO interference, and a mitochondrial membrane potential sufficient to drive uptake. Everything else is packaging.

SS-31's future in clinical medicine remains uncertain as of 2026. Stealth BioTherapeutics' Phase 3 trial in primary mitochondrial myopathy (MMPOWER-3) met its primary endpoint in 2020, but the FDA requested additional data before approval. The cardiolipin-stabilising mechanism is sound, the preclinical evidence is compelling across ischemia-reperfusion injury, heart failure, and neurodegenerative models, and the safety profile in humans has been clean through Phase 2. Whether it clears regulatory hurdles depends on endpoint selection and trial design, not the science of the peptide itself. For researchers exploring mitochondrial therapeutics, SS-31 remains the reference standard for cardiolipin-targeted intervention. Just make sure the sequence on your certificate of analysis matches D-Arg-Dmt-Lys-Phe-NH₂, regardless of what abbreviation the supplier uses.

If the molecule interests you for mitochondrial bioenergetics research, you can explore high-purity preparations across our full peptide collection. Every batch synthesised to exact amino-acid sequencing with third-party verification.

Questions

Yes — SS31 and SS-31 are identical. Both refer to the tetrapeptide sequence D-Arg-Dmt-Lys-Phe-NH₂, also known as Elamipretide or MTP-131. The hyphen in SS-31 was added by some researchers as a typographic convention to separate the ‘SS’ abbreviation (Szeto-Schiller peptide series) from the numeric identifier ’31’, but no structural, mechanistic, or functional difference exists between the two naming forms.

The names reflect different stages of the peptide’s development and publication history. SS-31 (or SS31) was the original lab designation from Hazel Szeto’s research group at Cornell University. MTP-131 (mitochondria-targeting peptide 131) was assigned when Stealth BioTherapeutics licensed the compound for clinical trials. Elamipretide is the International Nonproprietary Name (INN) designated by the World Health Organization in 2015, now used in regulatory and clinical contexts. All names describe the same molecule: D-Arg-Dmt-Lys-Phe-NH₂.

SS-31 binds with high affinity (Kd ~20 nM) to cardiolipin, a phospholipid unique to the inner mitochondrial membrane that anchors electron transport chain supercomplexes. By inserting its dimethyltyrosine residue into the cardiolipin headgroup, SS-31 prevents oxidative damage to cardiolipin’s acyl chains, preserving supercomplex stability. This keeps electron transfer efficient and reduces reactive oxygen species production at the source — a 2014 study showed 78% reduction in cardiolipin peroxidation with 10 µM SS-31 under oxidative stress.

No — SS-31 and MitoQ have fundamentally different mechanisms. SS-31 stabilises cardiolipin structure to preserve electron transport chain function, while MitoQ delivers a ubiquinone moiety to the mitochondrial matrix where it acts as a ROS scavenger. SS-31 targets the structural cause of mitochondrial dysfunction; MitoQ addresses a downstream effect. Their efficacy profiles differ significantly across disease models, and direct substitution in protocols is not appropriate without re-validation.

Reconstitute SS-31 in sterile water or phosphate-buffered saline (pH 7.4) at concentrations between 1–10 mM. Aliquot into single-use volumes and store at -20°C to avoid repeated freeze-thaw cycles, which degrade bioactivity by 20–30% after three cycles. The peptide is stable for 72 hours at 4°C in aqueous solution and at least 6 months when lyophilised at -20°C. Avoid DMSO as a solvent in cell culture work — concentrations above 0.5% v/v disrupt mitochondrial membrane potential and confound SS-31’s mechanism.

Request a certificate of analysis (COA) that includes HPLC chromatography and mass spectrometry data. The MS should confirm the expected molecular weight (640.4 Da for the free base form of D-Arg-Dmt-Lys-Phe-NH₂) and the HPLC should show >95% purity at 220 nm. The amino acid sequence must explicitly read D-Arg-2′,6′-dimethyltyrosine-Lys-Phe-NH₂ — trade names like ‘SS-31’ or ‘Elamipretide’ on the label are insufficient without sequence confirmation. Purity below 95% or unverified sequence indicates substandard synthesis.

Most published studies use SS-31 concentrations between 1–10 µM in cell culture to demonstrate cardiolipin protection and ROS reduction. At 10 µM, the peptide achieves ~1,000-fold accumulation in mitochondria relative to the cytosol due to the mitochondrial membrane potential. Lower concentrations (0.1–1 µM) are sometimes sufficient in highly polarised cells like cardiomyocytes, while depolarised or dysfunctional mitochondria may require 10–50 µM for comparable uptake. Dose-response curves should be established for each cell type.

Yes — SS-31 (as Elamipretide) completed Phase 2 trials in Barth syndrome, primary mitochondrial myopathy, and heart failure with preserved ejection fraction. Stealth BioTherapeutics’ Phase 3 trial in mitochondrial myopathy (MMPOWER-3) met its primary endpoint in 2020, but the FDA requested additional data before approval. As of 2026, the peptide has not received regulatory approval for any indication, though the safety profile through Phase 2 has been favourable with predominantly mild gastrointestinal and injection-site adverse events.

The 2′,6′-dimethyltyrosine residue in position 2 of the SS-31 sequence is the functional anchor that binds to cardiolipin’s headgroup region. Its bulky aromatic structure with methyl substitutions provides both hydrophobic interaction with the lipid bilayer and steric protection against oxidative degradation. Substituting Dmt with standard tyrosine reduces cardiolipin binding affinity by >10-fold and eliminates most of the peptide’s protective effects in ischemia-reperfusion models, as demonstrated in structure-activity relationship studies from the Szeto lab.

Both are salt forms of the same peptide used to balance positive charges during synthesis and lyophilisation. SS-31 acetate uses acetate as the counterion, while SS-31 TFA uses trifluoroacetate. The active peptide sequence (D-Arg-Dmt-Lys-Phe-NH₂) is identical in both. Acetate salts are preferred for some applications because residual TFA can interfere with mass spectrometry and may cause mild toxicity in cell culture at high peptide concentrations (>100 µM). Functionally, both forms perform equivalently when reconstituted at working concentrations (1–10 µM).

RESEARCH USE ONLY · NOT EVALUATED BY THE FDA