05 Apr 2026Updated 05 Apr 2026Research use only

Ss 31 Elamipretide Research

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SS-31 (Elamipretide): Mitochondrial Membrane Research

SS-31, also known as Elamipretide or MTP-131, is a synthetic tetrapeptide studied in laboratory settings for its role in mitochondrial membrane biology, cardiolipin interactions, and oxidative stress research. It belongs to the Szeto-Schiller (SS) peptide class, a family of mitochondria-targeted peptides designed to concentrate in the inner mitochondrial membrane.

SS-31 (Elamipretide): Mitochondrial Inner Membrane Targeting

SS-31 peptide D-Arg — Dmt — Lys — Phe-NH2 alternating +/aromatic Inner mitochondrial membrane Cardiolipin-rich bilayer ETC Complex I, III, IV Research outcomes Reduced cardiolipin oxidation Improved OXPHOS efficiency Cardiolipin peroxidation cytochrome c release, apoptosis inhibits MW: 664.84 g/mol — CAS: 736992-21-5 — D-Arg-Dmt-Lys-Phe-NH2 Research use only. Not for human or veterinary use.

Chemical and Molecular Data

Property Value
Molecular formula C32H52N12O6
Molecular weight 664.84 g/mol
CAS number 736992-21-5
Sequence D-Arg-Dmt-Lys-Phe-NH2
Amino acid count 4
Non-natural residues D-Arg (pos. 1), Dmt (2,6-dimethyltyrosine, pos. 2)
Peptide class Szeto-Schiller (SS) peptide
Purity greater than or equal to 98% as verified by HPLC
Form Lyophilised powder
Storage -20 degrees C, protected from light and moisture
Reconstitution Sterile water recommended

SS-31 (Elamipretide): Mitochondrial Inner Membrane Targeting

SS-31 tetrapeptide D-Arg — Dmt — Lys — Phe-NH2 Alternating +/aromatic motif Inner mitochondrial membrane Cardiolipin-rich bilayer ETC Complex I, III, IV site Research outcomes Reduced cardiolipin oxidation Improved OXPHOS efficiency Cardiolipin peroxidation Blocked by SS-31 binding MW: 664.84 g/mol — CAS: 736992-21-5 — Szeto-Schiller peptide class

Structural Design and Mitochondrial Targeting

SS-31 is designed with an alternating aromatic-cationic motif. The alternating pattern of aromatic (Dmt, Phe) and cationic (D-Arg, Lys) residues gives the peptide amphipathic properties critical for its interaction with the inner mitochondrial membrane.

Critically, SS-31 concentrates in the inner mitochondrial membrane independently of membrane potential, unlike many other mitochondrial-targeting molecules (such as triphenylphosphonium-conjugated compounds). This makes SS-31 useful for studying mitochondrial function in compromised or depolarised mitochondria — conditions found in ischaemia-reperfusion injury, heart failure, and ageing research models.

Cardiolipin Biology Research

The primary mechanistic focus in SS-31 research is its interaction with cardiolipin — a unique phospholipid found almost exclusively in the inner mitochondrial membrane. Cardiolipin is essential for the organisation and function of the electron transport chain, particularly cytochrome c anchoring and Complex I, III, and IV activity.

Laboratory research has examined SS-31's effects on cardiolipin organisation and oxidation. Under oxidative stress conditions, cardiolipin can become peroxidised and release cytochrome c from the inner membrane, initiating apoptosis. SS-31 has been studied for its ability to interact with cardiolipin and protect it from peroxidation in cell and mitochondria isolation models.

Electron Transport Chain Research

Research has examined SS-31's effects on electron transport chain efficiency and reactive oxygen species (ROS) production. Studies in isolated mitochondria and cell culture models have investigated changes in oxygen consumption rate, ATP production, and ROS output following SS-31 treatment. This connects SS-31 research to broader mitochondrial biology studies relevant to MOTS-c and NAD+ research.

SS Peptide Family Comparison

Peptide Sequence Net charge Cardiolipin affinity Primary research
SS-02 Dmt-D-Arg-Phe-Lys-NH2 +3 High Mitochondrial targeting
SS-20 Phe-D-Arg-Phe-Lys-NH2 +3 Moderate Antioxidant research
SS-31 (Elamipretide) D-Arg-Dmt-Lys-Phe-NH2 +3 Very high Cardiolipin / OXPHOS

Cardiolipin Biology: Why It Matters

Cardiolipin is unique among mammalian phospholipids: it has four acyl chains (making it a dimeric phospholipid), is found almost exclusively in the inner mitochondrial membrane, and is essential for the organisation and stability of the electron transport chain supercomplexes.

Key cardiolipin research areas relevant to SS-31 studies include:

  • ETC supercomplex assembly. Cardiolipin acts as a molecular glue holding respiratory chain complexes (CI, CIII, CIV) together into supercomplexes (also called respirasomes). These assemblies increase OXPHOS efficiency and reduce electron leak that generates ROS. SS-31's interaction with cardiolipin has been studied in the context of supercomplex stability.
  • Cytochrome c binding. In healthy mitochondria, cytochrome c is anchored to the inner membrane by cardiolipin interaction. When cardiolipin is peroxidised by ROS, cytochrome c dissociates and is released to the cytoplasm, initiating the intrinsic apoptosis cascade. SS-31 research has examined whether cardiolipin binding can prevent this peroxidation-induced release.
  • ATP synthase. Cardiolipin is required for the proper folding and dimerisation of ATP synthase (Complex V), and SS-31's effects on ATP production have been studied in this context.

Frequently Asked Questions

Why does SS-31 concentrate in the inner mitochondrial membrane without a membrane potential?
Most mitochondrially targeted compounds (such as triphenylphosphonium or MitoQ) rely on the large negative mitochondrial membrane potential (approximately -180 mV) to drive their accumulation in the mitochondrial matrix. SS-31 does not require membrane potential for inner membrane targeting — instead, it is driven by electrostatic and hydrophobic interactions with cardiolipin itself. This means SS-31 can concentrate at its target site even in depolarised mitochondria (as occur in ischaemia and in pathological states), making it a distinctive research tool for studying mitochondrial biology under stress conditions.

Published Research References

Szeto HH. "First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics." British Journal of Pharmacology, 2014. PMID: 23991888
Birk AV, et al. "The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin." JASN, 2013. PMID: 23744003
Szeto HH, Schiller PW. "Novel therapies targeting inner mitochondrial membrane." Pharmaceutical Research, 2011. PMID: 21110230

For laboratory and analytical research purposes only. Not for human or veterinary use. No dosage or administration guidance is provided or implied.

Related research compounds: MOTS-c | NAD+ | SLU-PP-332

View SS-31 product page

Disclaimer: Research use only. Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent disease.

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