What Is SS-31? Research Guide
Definition
SS-31, international nonproprietary name elamipretide, is a synthetic cell-permeable tetrapeptide: D-Arg-2',6'-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine (CAS 736992-21-5, C32H49N9O5, 639.8 Da). It comes from the Szeto-Schiller peptide series and appears in older papers as MTP-131 or Bendavia. Its target is not a receptor but a phospholipid — cardiolipin, in the inner mitochondrial membrane.
Key Takeaways
- →SS-31, international nonproprietary name elamipretide, is a synthetic cell-permeable tetrapeptide: D-Arg-2',6'-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine (CAS 736992-21-5, C32H49N9O5, 639.8 Da). It comes from the Szeto-Schiller peptide series and appears in older papers as MTP-131 or Bendavia.
- →Available for in-vitro research at ≥99% HPLC-verified purity from Peptide.Express.
- →Certificate of Analysis included with every order. Same-day US shipping.
SS-31 Specifications
| Property | Value |
|---|---|
| Compound | SS-31 |
| CAS Number | 736992-21-5 |
| Molecular Formula | C32H49N9O5 |
| Molecular Weight | 639.8 Da |
| Sequence / Structure | D-Arg-2',6'-Dmt-Lys-Phe-NH2 (cell-permeable tetrapeptide) |
| Mechanism Class | Cardiolipin-binding inner-mitochondrial-membrane protective peptide |
| Purity | ≥99% by HPLC, batch-specific CoA included |
Registry records for SS-31: PubChem
SS-31 Mechanism of Action
Cardiolipin is a four-tailed, cone-shaped phospholipid found almost nowhere outside the inner mitochondrial membrane, where it curves the membrane into cristae and holds the respiratory complexes together as supercomplexes. SS-31 binds it electrostatically: the cationic D-Arg and Lys side chains meet the phosphate headgroups while the dimethyltyrosine inserts into the acyl region. What that binding buys is protection from peroxidation. Oxidized cardiolipin stops organizing supercomplexes, electron leak rises, and the reactive oxygen species produced go on to oxidize more cardiolipin — a loop rather than a single insult. SS-31 interrupts it at the lipid instead of scavenging radicals afterwards, which is the distinction from a conventional antioxidant. The alternating aromatic-cationic pattern also means accumulation does not depend on membrane potential, so the peptide reaches depolarized mitochondria that potential-driven carriers cannot. Against that clean organelle-level account sits a hard translational record: Phase 2 and Phase 3 programmes in Barth syndrome and primary mitochondrial myopathy have run for years, reported mixed results on their primary endpoints, and produced no approval. The bioenergetic mechanism is a mechanism. It is not a proxy for a functional outcome.
SS-31 Research Applications
Extracellular flux respirometry, reading basal respiration, maximal respiration and spare respiratory capacity in cells put under an oxidative or ischemic insult.
Cardiolipin lipidomics. Mass spectrometry that resolves native from oxidized cardiolipin species is the most direct test of the proposed mechanism, and it is worth running before any functional endpoint is interpreted rather than after.
Supercomplex assembly by blue native PAGE of digitonin-solubilized mitochondria, which shows respirasome organization directly instead of inferring it from a respiration rate.
Comparison against substrate-supply approaches such as NAD+. Protecting the membrane and replacing a consumed coenzyme are different interventions, and a single functional readout will not tell them apart without separate arms.
SS-31 Storage Requirements
Store lyophilized SS-31 at -20°C (-4°F), desiccated and protected from light. Reconstituted, hold at 2-8°C (36-46°F), use within 14 to 28 days, and do not freeze the solution. The D-arginine at the N-terminus and the C-terminal amide block the exopeptidases that clear an ordinary tetrapeptide within minutes, so this molecule is unusually durable for its size — which means the thing to scrutinize on a certificate of analysis is identity rather than stability. A synthesis that used L-arginine or unmethylated tyrosine would land at a very similar mass and behave differently, so read the chromatographic trace alongside the mass number.
SS-31 at Peptide.Express
All SS-31 sold by Peptide.Express is HPLC-verified at ≥99% purity with a Certificate of Analysis included. Same-day US shipping on orders before 2 PM EST. For in-vitro laboratory research use only.
View SS-31 Product DetailsFrequently Asked Questions
What is SS-31?
SS-31 is a synthetic, cell-permeable tetrapeptide — D-Arg-2',6'-Dmt-Lys-Phe-NH2 — that binds cardiolipin in the inner mitochondrial membrane. Its CAS registry number is 736992-21-5, its molecular formula is C32H49N9O5 and its average molecular weight is 639.8 Da. It is studied in mitochondrial bioenergetics and oxidative-stress models, for laboratory research only.
Is SS-31 the same thing as elamipretide?
Yes. Elamipretide is the international nonproprietary name for the same molecule; SS-31 is its designation within the Szeto-Schiller peptide series, and MTP-131 and Bendavia are development codes for it. One CAS number, 736992-21-5, covers all four names. Papers use them interchangeably, which makes literature searches on this compound easy to under-collect.
How is SS-31 different from a conventional antioxidant?
Where it acts. A conventional antioxidant scavenges reactive oxygen species after they form. SS-31 binds cardiolipin and protects it from peroxidation, which interrupts the loop earlier: oxidized cardiolipin disorganizes respiratory supercomplexes, that disorganization increases electron leak, and the leak generates more oxidants. Acting on the lipid addresses the source of the cycle rather than its output.
Why does SS-31 contain non-standard amino acids?
Two of the four positions are unnatural for specific reasons. The D-configuration arginine at the N-terminus and the C-terminal amide together block the aminopeptidases and carboxypeptidases that would clear an ordinary tetrapeptide within minutes. The 2',6'-dimethyltyrosine supplies the aromatic bulk that inserts into the membrane acyl region, and the alternating aromatic-cationic pattern is what lets the peptide accumulate in mitochondria without depending on membrane potential.
Is SS-31 FDA approved?
No. Elamipretide has been evaluated in Phase 2 and Phase 3 trials in Barth syndrome and primary mitochondrial myopathy, and it holds no FDA approval for any indication. Years of trials without an approval is itself informative: a mechanism that behaves cleanly in isolated mitochondria has repeatedly proven harder to convert into a clinical endpoint. Peptide.Express supplies SS-31 for in-vitro laboratory research only.
Where can I buy SS-31 for research?
Research-grade SS-31 (elamipretide) is available from Peptide.Express at ≥99% HPLC-verified purity with LC-MS/MS mass confirmation and a batch-specific Certificate of Analysis. Visit peptide.express/catalog/ss-31 for full specifications.
References
- Birk AV, Liu S, Soong Y, Mills W, Singh P, Warren JD, Seshan SV, Pardee JD, Szeto HH. "The Mitochondrial-Targeted Compound SS-31 Re-Energizes Ischemic Mitochondria by Interacting with Cardiolipin." Journal of the American Society of Nephrology. 2013. Read the Birk 2013 SS-31 cardiolipin binding mechanism study
- Paradies G, Paradies V, De Benedictis V, Ruggiero FM, Petrosillo G. "Functional Role of Cardiolipin in Mitochondrial Bioenergetics." Biochimica et Biophysica Acta (Bioenergetics). 2014. Read the Paradies 2014 cardiolipin bioenergetics review
- FDA drug approvals and databases. Elamipretide does not appear as an approved drug product, which is the primary source for the regulatory statement on this page. Search the FDA drug approval databases
Research Areas Using SS-31
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How This Page Is Sourced
Molecular identity on this page — name, CAS number, molecular formula and molecular weight — is resolved from a single internal entity record and checked against primary registries (PubChem, CAS Common Chemistry) rather than retyped per page. A field with no verified value is left out instead of estimated. Literature is cited to a DOI, PMID or PMCID permalink so every reference resolves to the specific record it names.