SS-31 (Elamipretide) Molecular Profile: Structure, Cardiolipin Binding & Mechanism

SS-31 is a synthetic mitochondria-targeting peptide that travels under an unusually large number of names, which is the first thing to get straight before reading any of the literature. SS-31 (the "Szeto-Schiller" laboratory designation), elamipretide (the international nonproprietary name), MTP-131 (the clinical development code) and Bendavia (an earlier program name) all refer to the same molecule. Papers from before roughly 2014 tend to use "SS-31"; clinical-trial publications use "elamipretide". They are identical.

This page is a structural and biochemical profile: what the molecule is, how it is built, and the mechanism by which it acts on the mitochondrion. It deliberately does not re-run the head-to-head against the other major mitochondrial research peptide — that side-by-side (encoding, size, target, mechanism, research areas) is already covered in detail. For "MOTS-c vs SS-31", see the dedicated comparison in the MOTS-c research guide →. Here the focus stays on SS-31's own chemistry.

ClassSS-31 belongs to the aromatic-cationic peptide (Szeto-Schiller, or "SS") family — short synthetic peptides with an alternating aromatic/basic residue motif engineered to cross membranes and concentrate inside mitochondria without a targeting carrier.

SS-31 is a tetrapeptide — just four amino-acid residues — with the sequence D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH₂ (commonly written D-Arg-Dmt-Lys-Phe-NH₂). Two structural features define it:

• Alternating aromatic and basic residues. The chain pairs basic, positively charged residues (D-arginine, lysine) with aromatic residues (the modified tyrosine "Dmt", and phenylalanine). This alternating cationic/aromatic motif is the structural signature of the Szeto-Schiller aromatic-cationic peptide class (Szeto, Br J Pharmacol 2014).
• A D-amino acid and a C-terminal amide. The N-terminal arginine is the D-stereoisomer (D-Arg) rather than the natural L-form, and the C-terminus is amidated (-NH₂). Both modifications make the peptide markedly more resistant to peptidase degradation than an ordinary L-amino-acid peptide of the same length.

The 2',6'-dimethyltyrosine ("Dmt") residue is a non-standard, methylated tyrosine — not a residue found in ordinary translated proteins — which is part of why SS-31 has to be chemically synthesised rather than expressed.

Note that supplied salt forms (for example an acetate or hydrochloride salt) carry additional counter-ions, so a vial's stated mass refers to peptide content rather than salt mass — relevant when calculating concentrations for research handling.

Most molecules that act inside mitochondria need a delivery strategy, because the inner mitochondrial membrane is one of the tightest barriers in the cell. SS-31's design solves this passively. Its cationic, aromatic structure lets it cross the plasma membrane and accumulate within mitochondria, and — importantly — it does so without depending on the mitochondrial membrane potential as its driving force (Tung et al., Int J Mol Sci 2025). That distinguishes it from classic "delivery-vector" cations (such as triphenylphosphonium-tagged compounds) whose accumulation is potential-driven and can therefore fall away exactly when mitochondria are depolarised and most stressed.

Once inside, SS-31 does not stay free in the matrix. It concentrates at the inner mitochondrial membrane, the membrane that houses the electron transport chain and that is folded into the structures called cristae. Its target there is a specific phospholipid: cardiolipin.

The defining molecular interaction of SS-31 is its selective binding to cardiolipin, a four-tailed anionic phospholipid that is found almost exclusively in the inner mitochondrial membrane. Cardiolipin is not a bystander lipid: it is structurally required for the curvature of cristae and it organises the respiratory-chain complexes (and supercomplexes) that carry out oxidative phosphorylation (Birk et al., J Am Soc Nephrol 2013).

SS-31 associates with cardiolipin through a combination of electrostatic and hydrophobic interactions — the cationic residues are attracted to cardiolipin's anionic head groups, while the aromatic residues insert into the lipid environment (Szeto, Br J Pharmacol 2014). The interaction is selective for cardiolipin over the other major membrane phospholipids, which is what concentrates the peptide where the respiratory machinery actually sits. Proteomic interaction mapping has confirmed that within mitochondria SS-31's primary partner is the cardiolipin-rich inner-membrane environment and the proteins embedded in it (Chavez et al., Proc Natl Acad Sci U S A 2020).

Why cardiolipin is the right targetBecause cardiolipin both shapes cristae and scaffolds the electron-transport-chain complexes, a molecule that binds and stabilises cardiolipin sits at the structural heart of mitochondrial energy production — rather than acting on a single enzyme or receptor downstream.

From its cardiolipin-binding starting point, SS-31's reported mechanism follows a structural logic:

1. Cristae stabilisation. By binding cardiolipin, SS-31 helps preserve the tightly folded cristae architecture of the inner membrane. Cristae geometry is not cosmetic — the folds concentrate the respiratory complexes and ATP synthase, so maintaining that geometry helps maintain the platform on which oxidative phosphorylation runs.
2. Support for electron transport. Because cardiolipin organises the electron-transport-chain complexes, stabilising the cardiolipin environment is associated in the literature with better-preserved electron flow and improved coupling of respiration to ATP production, particularly in stressed or ischaemic mitochondria.
3. Reduced reactive oxygen species (ROS). When electron transport is poorly organised, electrons "leak" and generate ROS. By supporting orderly electron flow, SS-31 is reported to reduce mitochondrial ROS generation rather than simply scavenging ROS after the fact.

The framing in the primary literature is that SS-31 is a cardiolipin-protective compound: it acts on the lipid scaffold of the inner membrane to keep the energy-producing apparatus structurally intact, which is mechanistically different from an enzyme inhibitor, a receptor agonist, or a free-radical scavenger.

Only a few handling-relevant physicochemical points can be stated with confidence, so this section stays narrow:

• Peptidase resistance. The D-arginine residue and C-terminal amidation make SS-31 more resistant to enzymatic breakdown than an unmodified L-peptide of similar length — a deliberate design feature of the aromatic-cationic class.
• Administration route in trials. In its clinical-research program, elamipretide has been administered subcutaneously (and intravenously in some study settings) rather than orally — consistent with it being a peptide that is not designed for oral bioavailability.
• Form supplied for research. Like other research peptides, SS-31 is supplied as a lyophilised powder requiring reconstitution with bacteriostatic water before laboratory use; reconstituted peptide solutions are stored refrigerated and used within a limited window. For the general procedure see the peptide reconstitution & storage guide → and the reconstitution calculator →.

Specific human half-life and exposure figures are not stated here because a single reliable value is not consistently reported; rather than risk an inaccurate number, the page omits it.

SS-31 has one of the better-documented clinical records of any peptide in the research space, under the name elamipretide. The verifiable highlights:

Two honest caveats keep this accurate: the mitochondrial-myopathy results were mixed (the large MMPOWER-3 trial missed its endpoints in the broad population), and the September 2025 approval is specific to Barth syndrome — it is not an approval for general or anti-ageing use. SS-31 sold for research is a laboratory reagent, not an approved medicine for the use cases researchers may be studying.

Is SS-31 the same thing as elamipretide?

Yes. SS-31, elamipretide, MTP-131 and Bendavia are four names for the same molecule. "SS-31" is the original Szeto-Schiller laboratory name; "elamipretide" is the international nonproprietary name used in clinical trials and regulatory filings.

What is SS-31's amino acid sequence?

SS-31 is a tetrapeptide: D-Arg-2',6'-dimethyltyrosine-Lysine-Phenylalanine-amide, written D-Arg-Dmt-Lys-Phe-NH₂. It uses a D-amino acid and a non-standard methylated tyrosine, which is why it must be chemically synthesised.

What is SS-31's molecular weight?

The free-base molecular formula is C₃₂H₄₉N₉O₅, giving a molecular weight of approximately 639.8 g/mol. Salt forms carry additional counter-ions, so the labelled peptide mass refers to peptide content, not total salt mass.

What does SS-31 bind to?

SS-31 selectively binds cardiolipin, an anionic phospholipid concentrated in the inner mitochondrial membrane, through combined electrostatic and hydrophobic interactions. Cardiolipin shapes cristae and organises the electron transport chain, which is why it is the target.

How does SS-31 differ from MOTS-c?

They are different classes of mitochondrial peptide acting on different targets — SS-31 is a synthetic structural tetrapeptide that binds cardiolipin in the inner membrane, while MOTS-c is a 16-amino-acid mitochondrial-DNA-encoded signalling peptide. The full side-by-side comparison lives in the MOTS-c research guide →.

Is SS-31 / elamipretide approved?

Elamipretide received US approval for Barth syndrome in September 2025. That approval is specific to Barth syndrome; SS-31 supplied as a research peptide is a laboratory reagent and is not an approved medicine for other uses. It is not TGA-approved and is not for human consumption.

OzPeps is an Australia-based supplier stocking research-grade SS-31 (elamipretide) as lyophilised 10mg vials for laboratory reconstitution, with domestic shipping (1–3 business days Australia-wide).

• Product: SS-31 10mg, lyophilised powder, single vial
• Shipping: Domestic Australia, 1–3 business days
• Payment: Cryptocurrency (Bitcoin, Monero, Litecoin)
• Supplies: Bacteriostatic water, insulin syringes and alcohol swabs also available

View SS-31 10mg stock and current pricing →

Related guide: MOTS-c research guide (includes the MOTS-c vs SS-31 comparison) →

SS-31 (elamipretide) is sold strictly for in-vitro laboratory research. Research-grade / research use only. Not TGA-approved for the uses discussed. Not for human or animal consumption. Nothing on this page is medical advice or a human-dosing recommendation; clinical-trial details are reported as published scientific record, not as usage guidance.