What Is SS-31? Elamipretide Structure, Data and Status

By Sequora Research Team · Updated October 2026

What is SS-31? It is a synthetic four-amino-acid peptide, D-Arg-Dmt-Lys-Phe-NH2, designed to concentrate in the inner mitochondrial membrane. It belongs to the Szeto-Schiller peptide family, and its international nonproprietary name is elamipretide [R1] [R2].

This monograph covers the SS-31 peptide on its own. It sets out structure, identifiers, mitochondrial targeting, research areas and regulatory status. For a comparison with a mitochondria-encoded peptide, see MOTS-c vs SS-31. For the wider class, read what mitochondrial peptides are.

SS-31 at a glance: structure and identifiers

“SS” refers to the Szeto-Schiller peptide series, a family of peptides that target the inner mitochondrial membrane [R2]. SS-31 is also written “SS 31” or “SS31.” In clinical development it carries the name elamipretide. The identifiers below are checked against PubChem [R1].

Two features stand out. The first residue is D-arginine, the mirror-image form of the usual L-arginine. The second is Dmt, a tyrosine with two extra methyl groups on its ring. Neither is a standard building block of natural proteins.

The C-terminal phenylalanine is an amide (-NH2) rather than a free acid. SS-31 is therefore a compact molecule with a molecular weight of 639.8 g/mol [R1].

The aromatic-cationic design

SS-31 alternates basic (positively charged) and aromatic residues. Arginine and lysine carry the positive charges. Dmt and phenylalanine provide the aromatic rings.

Mitchell et al. described this as an alternating cationic-aromatic register [R4]. The motif is thought to help such peptides cross membranes and concentrate in mitochondria.

The same study compared SS-31 with related tetrapeptides. It reported that SS-31 stays in an extended shape when bound to membranes. The authors attributed this to the methyl groups on Dmt, which block a folded “reverse-turn” shape [R4].

How SS-31 compares with its analogs

Mitchell et al. tested SS-31 against tetrapeptides that share its building blocks in a different order [R4]. Every analog bound membranes that contained cardiolipin. SS-31 bound with an affinity similar to the others.

The difference lay in stoichiometry, meaning how many peptide molecules associated with the lipid. SS-31 differed from the analogs on this measure [R4].

The authors also cited earlier work from the group. That work suggested SS-31 acts partly by changing the surface electrical potential of the membrane [R4]. For researchers, the point is practical: residue order and Dmt methylation both shape how these peptides sit in a membrane.

How SS-31 reaches mitochondria and binds cardiolipin

Cell permeability

Many peptides cannot cross cell membranes on their own. SS-31 is an exception. In cultured human kidney (HK-2) and retinal (ARPE-19) cells, Mitchell et al. reported that SS-31 entered both cell lines within an hour [R4]. Inside the cells, it showed a mitochondrial localization pattern.

Selective concentration in the inner mitochondrial membrane

In a 2014 review, Szeto described the SS peptides as selectively targeting the inner mitochondrial membrane [R2]. The review links this site to oxidative phosphorylation, the process that produces most cellular ATP.

Cardiolipin binding

Cardiolipin is an anionic phospholipid expressed on the inner mitochondrial membrane [R3]. Szeto’s review ties it to the structure of cristae, the folds of that membrane [R2].

Birk et al. reported that SS-31 bound cardiolipin with high affinity [R3]. They used a polarity-sensitive fluorescent analog of SS-31 to show the interaction. The SS-31/cardiolipin complex inhibited the peroxidase activity of cytochrome c, an activity that oxidizes cardiolipin during ischemia.

Szeto’s review summarized the proposed mechanism. Binding is driven by electrostatic and hydrophobic interactions. It is proposed to limit cytochrome c peroxidase activity while preserving its role as an electron carrier [R2].

Research areas studied

The sections below describe research areas and the models used. They are not statements of effect in people.

In the rat kidney study, Birk et al. reported preserved cristae and less mitochondrial swelling during ischemia [R3]. They also reported faster ATP recovery on reperfusion. These are rat findings and should not be extrapolated to people.

FDA describes Barth syndrome as a rare, serious, life-threatening mitochondrial disease [R5]. A 2025 review called elamipretide the first cardiolipin-directed mitochondrial therapeutic approved for it [R6].

Regulatory status: elamipretide and FDA, plus WADA

FDA

On September 19, 2025, FDA granted accelerated approval to elamipretide for Barth syndrome, in patients weighing at least 30 kg [R5]. FDA described it as the first approved drug for the condition.

Accelerated approval rests on a surrogate measure that FDA considers reasonably likely to predict clinical outcomes. Here the measure was knee extensor muscle strength. FDA requires a randomized, double-blind, placebo-controlled confirmatory trial after approval [R5]. Because accelerated approvals can change, check FDA’s current status for elamipretide before citing it.

This approval covers one finished drug product for one indication. It does not apply to research-grade SS-31, which is sold for laboratory use only.

WADA

Neither SS-31 nor elamipretide is named on the WADA 2026 Prohibited List [R7]. The list gives examples within each class, so a substance not named there is not automatically permitted. Athletes should confirm status with their anti-doping organization.

SS-31 for laboratory research

Sequora supplies SS-31 (10 mg) for in vitro and laboratory research only, within our mitochondrial peptides collection. We do not provide dosing, administration or use guidance of any kind.

Each vial is lyophilized, sealed and labelled with a batch code. Each batch is third-party tested by HPLC for purity and by mass spectrometry for identity. The COA for any batch is available by email at research@sequorapeptides.com.

For SS-31, the mass spectrometry identity reading should match the expected mass near 639.8 Da. Our guide on how to read a peptide COA explains each section. Orders ship to the US and Canada.

SS-31 Peptide FAQ

Is SS-31 the same as elamipretide?

Yes. Elamipretide is the international nonproprietary name for SS-31, with the same structure, D-Arg-Dmt-Lys-Phe-NH2 [R1].

What does SS-31 bind to?

Birk et al. reported high-affinity binding to cardiolipin, a phospholipid of the inner mitochondrial membrane [R3].

Is SS-31 cell-permeable?

In cultured HK-2 and ARPE-19 cells, SS-31 entered both cell lines within an hour and localized to mitochondria [R4].

Is elamipretide FDA approved?

FDA granted accelerated approval on September 19, 2025, for Barth syndrome in patients weighing at least 30 kg [R5]. A confirmatory trial is required.

What is the molecular weight of SS-31?

PubChem lists 639.8 g/mol for the formula C32H49N9O5 [R1].

How is SS-31 different from MOTS-c?

SS-31 is a synthetic tetrapeptide aimed at the inner mitochondrial membrane. MOTS-c is a natural 16-residue peptide encoded by mitochondrial DNA. See what MOTS-c is for its monograph.

References

1. National Center for Biotechnology Information. PubChem Compound Summary for CID 11764719, Elamipretide. pubchem.ncbi.nlm.nih.gov/compound/11764719.
2. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029–2050. doi:10.1111/bph.12461.
3. 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. J Am Soc Nephrol. 2013;24(8):1250–1261. doi:10.1681/ASN.2012121216. PMID 23813215.
4. Mitchell W, Tamucci JD, Ng EL, Liu S, Birk AV, Szeto HH, May ER, Alexandrescu AT, Alder NN. Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds. eLife. 2022;11:e75531. doi:10.7554/eLife.75531.
5. U.S. Food and Drug Administration. FDA grants accelerated approval to first treatment for Barth syndrome. Press announcement, September 19, 2025. fda.gov.
6. Zhao C, Zhuang X, Gao J. Elamipretide: the first cardiolipin-directed mitochondrial therapeutic for Barth syndrome approved under accelerated approval. Drug Discov Ther. 2025;19(6). doi:10.5582/ddt.2025.01111.
7. World Anti-Doping Agency. The Prohibited List (2026). wada-ama.org/en/prohibited-list.

For laboratory research use only. Not for human or veterinary use.