SS-31

SS-31 (elamipretide) is a synthetic, amphipathic tetrapeptide from the Szeto-Schiller (SS) peptide family, which targets the inner mitochondrial membrane. Its sequence includes D-arginine and 2′,6′-dimethyltyrosine (Dmt). Research on the SS-31 peptide has focused on its binding to cardiolipin, the phospholipid that shapes mitochondrial cristae, and on what that binding does to cytochrome c peroxidase activity, ATP recovery after renal ischemia in rats, membrane surface electrostatics and contacts with oxidative phosphorylation proteins. Research Market supplies SS-31 with purity and identity data for each lot reported on its certificate of analysis. It is sold strictly for laboratory research use.

Chemical structure and identification

• Molecular formula: C₃₂H₄₉N₉O₅
• Molecular weight: 639.8 g/mol
• CAS number: 736992-21-5
• PubChem CID: 11764719
• Amino acid sequence: D-Arg-Dmt-Lys-Phe-NH₂ (Dmt = 2′,6′-dimethyltyrosine)
• Synonyms: Elamipretide, MTP-131, SS 31
• Form: Lyophilized powder
• Analytical methods: RP-HPLC for purity and mass spectrometry for identity, reported on the batch certificate of analysis

Research applications

• Cardiolipin binding: Reviewed as binding cardiolipin selectively through electrostatic and hydrophobic interactions, which keeps cardiolipin from converting cytochrome c into a peroxidase while preserving its electron-carrier role [1]
• Renal ischemia: A polarity-sensitive fluorescent analog showed high-affinity binding to cardiolipin; in rats, pretreatment protected cristae membranes during renal ischemia, with no mitochondrial swelling, and ATP recovered promptly on reperfusion [2]
• Membrane biophysics: In model and mitochondrial membranes, SS-31 partitioned into the interfacial region in proportion to surface charge, altered lipid packing without destabilizing bilayers, modulated surface electrostatics and changed calcium distribution at the interface [3]
• Mitochondrial protein interactions: Chemical cross-linking with mass spectrometry identified SS-31-interacting proteins in mitochondria, all known cardiolipin binders, involved in oxidative phosphorylation and 2-oxoglutarate metabolism [4]

Reference citations

1. Szeto H.H. (2014). First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol, 171(8):2029–2050. PMID 24117165 · DOI
2. Birk A.V. et al. (2013). The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol, 24(8):1250–1261. PMID 23813215 · DOI
3. Mitchell W. et al. (2020). The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. J Biol Chem, 295(21):7452–7469. PMID 32273339 · DOI
4. Chavez J.D. et al. (2020). Mitochondrial protein interaction landscape of SS-31. Proc Natl Acad Sci U S A, 117(26):15363–15373. PMID 32554501 · DOI

Compound data from PubChem CID 11764719. Literature summaries describe published preclinical research and are not claims about this product’s effects in humans or animals.