Expand Image

≥99% PurityUS SynthesizedIn Stock

SS-31 (Elamipretide) — Cardiolipin-Binding Mitochondrial Tetrapeptide | D-Arg-Dmt-Lys-Phe-NH2 Research Compound

Research-Grade Compound

SS-31 (elamipretide) is a synthetic, cell-permeable tetrapeptide that binds cardiolipin in the inner mitochondrial membrane. Sequence: D-Arg-2',6'-Dmt-Lys-Phe-NH2, where 2',6'-Dmt is 2',6'-dimethyltyrosine, a non-proteinogenic aromatic residue. Molecular formula C32H49N9O5, molecular weight 639.8 Da, CAS 736992-21-5. It belongs to the Szeto-Schiller (SS) peptide series developed by Hazel Szeto and Peter Schiller, and also appears in the literature under the development codes MTP-131 and Bendavia.

Purity standard: SS-31 is sourced to ≥99% by HPLC. That is the specification every batch must meet, not a measurement of any one vial — the measured figure for a batch is on that batch's Certificate of Analysis.

Select Size

$55.00$75.00USD / Unit

HPLC Verified

Same Day Shipping

Showing CoA for 10mg

Certificate Details

Purity≥99%

Methodology

HPLCLC-MS/MS

CAS Number736992-21-5

Molecular FormulaC32H49N9O5

Molecular Weight639.8 g/mol

SequenceD-Arg-2',6'-Dmt-Lys-Phe-NH2 (cell-permeable tetrapeptide)

Download PDF Open in New Tab

This Certificate of Analysis was issued by an independent third-party laboratory. Peptide.Express does not conduct in-house testing. Results are provided as-is from the testing facility and confirm batch identity, purity, and analytical methodology. For questions about specific CoA results, contact support@peptide.express.

Safety Data Sheet (SDS)

≥99% by HPLCLC-MS/MS VerifiedCoA Every BatchIn-Vitro Research Use Only

What is SS-31?

Two structural features do most of the work. The alternating aromatic-cationic motif gives the molecule its mitochondrial affinity without depending on membrane potential, so it accumulates in mitochondria that are already depolarized — precisely the mitochondria that most mitochondria-targeted compounds cannot reach. And the D-configuration arginine at the N-terminus plus the C-terminal amide make it resistant to the aminopeptidases and carboxypeptidases that clear ordinary tetrapeptides in minutes.

Elamipretide has been through a longer clinical development programme than almost anything else in this catalog, with Phase 2 and Phase 3 trials in Barth syndrome and primary mitochondrial myopathy. It is not FDA-approved for any indication. That combination — years of trials, no approval — is itself information, and researchers reading the preclinical literature should hold it in mind: a mechanism that is clean in isolated mitochondria has repeatedly proven harder to convert into a clinical endpoint in patients.

How Does SS-31 Work? Mechanism of Action

Cardiolipin is the target, and cardiolipin is unusual. It is a dimeric phospholipid with four acyl chains and a conical shape, found almost exclusively in the inner mitochondrial membrane, where it makes up roughly a fifth of the phospholipid content. Its job is structural and organizational: cardiolipin curves the membrane into cristae and holds the electron transport chain complexes together into supercomplexes — the respirasomes that let electrons pass between Complex I, III and IV without escaping into the matrix.

SS-31 binds cardiolipin through electrostatic contact between its cationic D-Arg and Lys residues and the phosphate headgroups, with the dimethyltyrosine inserting into the hydrophobic region. The functional consequence is protection of cardiolipin from peroxidation. Oxidized cardiolipin no longer organizes supercomplexes properly; electron leak rises, reactive oxygen species production rises with it, and the process becomes self-reinforcing because the ROS oxidize more cardiolipin. Binding interrupts that loop rather than scavenging the ROS after the fact, which is the distinction between SS-31 and a conventional antioxidant.

Downstream, preclinical work reports maintained mitochondrial membrane potential, preserved ATP synthesis capacity, stabilized cristae ultrastructure on electron microscopy, and reduced release of cytochrome c — which matters because cytochrome c leaving the intermembrane space is an apoptotic trigger. Cardiolipin also anchors cytochrome c to the membrane in the first place, so a compound that protects cardiolipin is acting on both the structural and the apoptotic arm through one interaction.

What the evidence does not settle is the gap between organelle and organism. Isolated-mitochondria and cell-culture results for SS-31 are consistent and mechanistically legible. Translation has been harder: clinical programmes in primary mitochondrial myopathy and Barth syndrome have run for years without producing an approval, and published trial outcomes have been mixed on their primary endpoints. Whatever the reason — effect size, endpoint selection, patient heterogeneity in mitochondrial disease — a research design should not treat the bioenergetic mechanism as a proxy for a functional outcome.

Research Applications of SS-31

Mitochondrial Bioenergetics Research

Oxygen consumption rate assays: Seahorse extracellular flux measurement of basal respiration, maximal respiration and spare respiratory capacity in treated cell populations.
Membrane potential quantification: TMRM or JC-1 fluorescence in models where depolarization is induced chemically or by substrate deprivation.
Supercomplex assembly: blue native PAGE of digitonin-solubilized mitochondria, which shows whether respirasome organization is preserved rather than inferring it from function.

Oxidative Stress and Cardiolipin Chemistry

Cardiolipin peroxidation profiling: mass spectrometric lipidomics distinguishing native from oxidized cardiolipin species, which is the most direct readout of the proposed mechanism.
Mitochondrial ROS measurement: MitoSOX and related probes, reported alongside cytosolic ROS so that compartment specificity can be demonstrated rather than assumed.
Cristae ultrastructure: transmission electron microscopy scoring of cristae density and organization in tissue from injury models.

Ischemia-Reperfusion and Mitochondrial Disease Models

Cardiac ischemia-reperfusion preparations: infarct size and post-ischemic contractile recovery in isolated perfused hearts, the setting where the SS peptide series was first characterized.
Renal and neuronal injury models: mitochondrial dysfunction as the shared upstream event across otherwise unrelated tissue injuries.
Genetic mitochondrial disease models: Barth syndrome cell lines carry a tafazzin defect that leaves cardiolipin remodeling incomplete, making them the mechanistically tightest system for testing a cardiolipin-binding compound.

SS-31 vs NAD+ for Mitochondrial Research

Feature	SS-31 (Elamipretide)	NAD+
Molecular class	Synthetic tetrapeptide	Dinucleotide coenzyme (not a peptide)
Molecular formula	C32H49N9O5	C21H27N7O14P2
Molecular weight	639.8 Da	663.4 Da
CAS number	736992-21-5	53-84-9
Molecular target	Cardiolipin, inner mitochondrial membrane	Complex I, sirtuins (SIRT1-7), PARPs, CD38
Type of intervention	Structural protection of an existing membrane	Replacement of a consumed substrate
Primary readout	ROS production, membrane potential, cristae structure	NAD+/NADH ratio, sirtuin deacylase activity
Endogenous?	No — fully synthetic	Yes — present in every living cell
Solution stability	Typical peptide: 14–28 days at 2–8°C	Short: use within 24–48 hours
Clinical development	Phase 2/3 trials completed; no FDA approval	No approval as an injectable drug product

These are complementary rather than competing tools, and the difference is worth being precise about. SS-31 protects the structure that the electron transport chain is built on. NAD+ replenishes the substrate that runs through it. A mitochondrion with intact cristae and no NAD+ produces nothing; so does one with abundant NAD+ and disorganized supercomplexes. Which compound belongs in a given study depends on whether the model damages the membrane or depletes the pool.

SS-31 Technical Specifications

Technical specifications for SS-31, including molecular data, purity standard, testing methods and storage requirements.
Compound Name	SS-31 (elamipretide)
Common Synonyms	Elamipretide, MTP-131, Bendavia, SS31, Szeto-Schiller 31
Classification	Szeto-Schiller aromatic-cationic tetrapeptide
Amino Acid Sequence	D-Arg-2',6'-Dmt-Lys-Phe-NH2
Amino Acid Count	4, including the non-proteinogenic residue 2',6'-dimethyltyrosine
CAS Number	736992-21-5
Molecular Formula	C32H49N9O5
Molecular Weight	639.8 Da
Molecular Target	Cardiolipin, inner mitochondrial membrane
Mitochondrial Uptake	Independent of membrane potential — accumulates in depolarized mitochondria
Clinical Status	Phase 2/3 clinical development (Barth syndrome, primary mitochondrial myopathy); not FDA-approved
Purity	≥99% by HPLC
Purity Confirmation	LC-MS/MS molecular weight verification
Endotoxin Testing	LAL (Limulus Amebocyte Lysate) method
Physical Form	Lyophilized powder
Appearance	White to off-white powder
Reconstitution	Bacteriostatic water or sterile 0.9% sodium chloride
Storage (lyophilized)	-20°C, desiccated, protected from light
Storage (reconstituted)	2–8°C, use within 14–28 days
Shelf Life	24 months from manufacture (lyophilized)
Testing Methods	HPLC, LC-MS/MS, LAL Endotoxin
Documentation	Certificate of Analysis (CoA) per batch
FDA Status	Not approved for human use; investigational
Intended Use	In-vitro laboratory research only

How to Reconstitute SS-31 for Research

SS-31 is a small, highly cationic peptide and it dissolves readily. The practical caution is adsorption rather than solubility: cationic peptides at low concentration stick to glass and to some plastics, and a dilute working solution can lose material to the container wall before it ever reaches the assay. Prepare a concentrated stock, dilute immediately before use, and keep low-binding tubes on hand if the assay runs in the micromolar range or below.

Allow the vial to reach room temperature before opening.
Draw the calculated volume of bacteriostatic water. For a 10 mg vial, 2 mL yields 5 mg/mL; for the 50 mg vial, 5 mL yields 10 mg/mL. At 639.8 Da, 5 mg/mL corresponds to approximately 7.8 mM.
Swab the septum with 70% isopropyl alcohol and allow 30 seconds to dry.
Inject the diluent slowly against the inner vial wall. Do not spray it onto the lyophilized cake.
Swirl for 30–60 seconds. This peptide dissolves quickly; extended agitation gains nothing and risks foaming.
Verify a clear, colorless solution with no particulate. Discard if cloudy or discolored.
Label with the reconstitution date, concentration in mg/mL, and the molar concentration if the assay works in molar terms — converting later from memory is where errors enter.
Store at 2–8°C and use within 14–28 days. Avoid repeated freeze-thaw cycles.

Diluent: bacteriostatic water for peptide reconstitution. Full protocol: step-by-step peptide reconstitution guide. Concentration maths: peptide reconstitution calculator.

Frequently Asked Questions — SS-31

What is SS-31 peptide?

SS-31 is a synthetic cell-permeable tetrapeptide, sequence D-Arg-2',6'-Dmt-Lys-Phe-NH2, molecular formula C32H49N9O5, molecular weight 639.8 Da, CAS 736992-21-5. It binds cardiolipin in the inner mitochondrial membrane and is studied in mitochondrial bioenergetics and oxidative stress models. Sold for in-vitro laboratory research use only.

Is SS-31 the same as elamipretide?

Yes. SS-31 is the research designation from the Szeto-Schiller peptide series; elamipretide is the international nonproprietary name assigned for clinical development. MTP-131 and Bendavia refer to the same molecule under earlier development codes.

What is cardiolipin and why does SS-31 bind it?

Cardiolipin is a dimeric phospholipid with four acyl chains, found almost exclusively in the inner mitochondrial membrane, where it accounts for roughly 20% of phospholipid content. It curves the membrane into cristae and holds electron transport chain complexes together into supercomplexes. When reactive oxygen species peroxidize cardiolipin, that organization degrades and electron leak increases. SS-31 binds cardiolipin electrostatically through its D-Arg and Lys residues, protecting it from peroxidation and preserving supercomplex structure.

How does SS-31 reach mitochondria?

Through its alternating aromatic-cationic structure, which drives accumulation in the inner mitochondrial membrane without requiring an intact membrane potential. That distinguishes it from potential-driven carriers such as triphenylphosphonium conjugates, which concentrate only in mitochondria that are still polarized — the healthy ones. SS-31 reaches damaged mitochondria, which is where the research question usually lives.

Is SS-31 FDA-approved?

No. Elamipretide is investigational. It has been through Phase 2 and Phase 3 clinical trials for Barth syndrome and primary mitochondrial myopathy, but it holds no FDA approval for any indication. Peptide.Express supplies it for in-vitro laboratory research only.

Is SS-31 in clinical trials?

It has been, extensively, over more than a decade — primary mitochondrial myopathy and Barth syndrome are the two programmes that ran furthest. Published outcomes have been mixed on primary endpoints, and no approval has followed. For a researcher, the useful takeaway is not that the mechanism is wrong but that the distance between a bioenergetic readout and a clinical functional endpoint is larger than the preclinical literature makes it look.

What is the difference between SS-31 and NAD+ for mitochondrial research?

SS-31 protects structure; NAD+ replaces substrate. SS-31 is a 639.8 Da synthetic tetrapeptide that binds cardiolipin and preserves cristae and supercomplex organization. NAD+ is a 663.4 Da dinucleotide coenzyme — not a peptide — that carries electrons into Complex I and serves as the consumed substrate for sirtuins and PARPs. They address different failure modes and can be run as separate arms in the same experiment.

What is the Szeto-Schiller peptide family?

A series of small aromatic-cationic peptides developed by Hazel Szeto and Peter Schiller, characterized by alternating aromatic and basic residues that produce mitochondrial accumulation without a potential requirement. SS-31 is the member that advanced furthest; SS-02 and SS-20 appear in the earlier mechanistic literature and differ in residue composition and in whether they bind cardiolipin.

Can SS-31 protect against ischemia-reperfusion injury in research models?

Ischemia-reperfusion is the model class where the SS peptide series was first characterized, and cardiac and renal preparations report reduced infarct size and better post-ischemic recovery. The mechanistic logic fits: reperfusion drives a burst of ROS that peroxidizes cardiolipin, and a cardiolipin-binding compound intercepts that step. The evidence is preclinical.

Why does SS-31 contain a D-amino acid?

The N-terminal arginine is in the D-configuration, and the C-terminus is amidated. Both modifications block the exopeptidases that would otherwise degrade a four-residue peptide within minutes. The 2',6'-dimethyltyrosine is a separate design choice — the methyl groups tune the aromatic character that drives membrane partitioning.

What purity standard does Peptide.Express use for SS-31?

≥99% by reverse-phase HPLC with LC-MS/MS confirming the 639.8 Da mass. The mass check matters more than usual here because SS-31 contains a non-standard residue and a D-amino acid — a synthesis that substituted L-arginine or plain tyrosine would produce a peptide of very similar mass but different behavior, so the chromatographic profile on the CoA is worth reading alongside the mass.

How should SS-31 be stored?

Lyophilized at -20°C, desiccated and light-protected, stable for 24 months. Reconstituted, at 2–8°C for 14–28 days. Do not freeze the reconstituted solution.

Where is the Certificate of Analysis for SS-31?

On this page and in the Peptide.Express lab results library, tied to the batch number printed on the vial label. Each CoA lists HPLC purity, LC-MS/MS mass confirmation, endotoxin result, testing laboratory and test date.

Research 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

All products are sold for in-vitro laboratory research use only. Not intended for human consumption, clinical use, or veterinary use. Peptide.Express makes no medical claims. Consult the published literature for research application guidance.