Elamipretide Triacetate: Key Facts & FAQs

Elamipretide triacetate is a salt form of the mitochondria-targeted aromatic-cationic tetrapeptide Elamipretide (also known as SS-31 or MTP-131), supplied as a research-grade reagent for studies of mitochondrial function, cardiolipin interaction, and oxidative stress.

Product Name

Elamipretide triacetate

SKU

E1439311

Also Known As

SS-31 triacetate; MTP-131 triacetate; Bendavia triacetate

Peptide Class

Aromatic-cationic, mitochondria-targeted tetrapeptide (Szeto-Schiller peptide)

Primary Target

Cardiolipin on the inner mitochondrial membrane

Key Research Applications

Mitochondrial bioenergetics, ROS attenuation, ischemia-reperfusion injury models, heart failure research

What Is Elamipretide Triacetate?

Elamipretide triacetate is the triacetate salt form of Elamipretide, a synthetic aromatic-cationic tetrapeptide belonging to the Szeto-Schiller (SS) peptide family. The parent compound, commonly designated SS-31 or MTP-131, carries the sequence D-Arg-dimethylTyr-Lys-Phe-NH₂. In its triacetate form, three acetate counterions neutralize the cationic charges of the peptide, improving physicochemical stability compared with the free-base peptide while retaining full biological activity in solution.

The compound selectively concentrates in the inner mitochondrial membrane (IMM) independently of mitochondrial membrane potential, a pharmacological feature that distinguishes it from earlier mitochondria-targeted antioxidants. Its primary molecular interaction is with cardiolipin, the signature phospholipid of the IMM, where it is proposed to stabilize cristae architecture and support the efficiency of electron transport chain (ETC) complexes.

Mechanism of Action

Elamipretide exerts its effects through two interrelated mechanisms:

• Cardiolipin binding: The alternating aromatic and cationic residues of the peptide interact electrostatically and hydrophobically with cardiolipin head groups, preventing cardiolipin peroxidation and preserving its role in organizing ETC supercomplexes (respirasomes).
• ROS scavenuation: The dimethyltyrosine residue confers intrinsic radical-scavenging capacity, reducing mitochondrial reactive oxygen species (ROS) generation without permanently depleting endogenous antioxidant pools.

Together these actions maintain the proton-motive force across the IMM, restore ATP synthesis rates under stress conditions, and attenuate apoptotic signaling triggered by cytochrome c release. Importantly, the mechanism is independent of membrane potential, making Elamipretide effective even in severely depolarized mitochondria.

Solubility, Storage, and Handling

Solubility: Elamipretide triacetate is freely soluble in water and aqueous buffers such as PBS, making aqueous stock solutions the preferred preparation route for in vitro and in vivo studies. DMSO can also be used as a co-solvent at low concentrations if required by the assay format.

Storage: Store the lyophilized powder at −20 °C, protected from light and moisture. Under recommended conditions, the compound is stable for at least 24 months from date of manufacture. Avoid repeated freeze-thaw cycles; aliquot stock solutions before freezing.

Reconstitution: Dissolve in sterile water or PBS to the desired concentration. Prepare working solutions fresh or store aliquots at −80 °C for short-term use. Filter-sterilize (0.22 µm) before cell-culture applications.

Note: Specific solubility values and certificate-of-analysis data are provided on the product datasheet for SKU E1439311. Always consult the CoA for lot-specific purity and analytical data.

Research Applications

Elamipretide triacetate is used across a broad range of preclinical research contexts:

• Ischemia-reperfusion injury (IRI): Applied in cardiac, renal, and cerebral IRI models to evaluate protection of mitochondrial integrity during reperfusion.
• Heart failure and cardiomyopathy: Used to study restoration of mitochondrial bioenergetics and cardiac contractile function in failing myocardium.
• Neurodegenerative disease models: Investigated for neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and optic neuropathy where mitochondrial dysfunction is implicated.
• Aging research: Studied as an intervention to reverse age-associated declines in mitochondrial function and skeletal muscle energetics.
• Rare mitochondrial diseases: Explored in Barth syndrome and primary mitochondrial myopathy research due to its direct cardiolipin-stabilizing activity.

Typical in vitro working concentrations range in the nanomolar to low-micromolar range; in vivo dosing regimens vary by model. Researchers should optimize concentrations empirically and consult primary literature for guidance.

Ordering and Product Information

Elamipretide triacetate is available from Aladdin Scientific under SKU E1439311. The product is supplied as a lyophilized powder with purity assessed by HPLC and identity confirmed by mass spectrometry. A certificate of analysis (CoA) is available for each lot upon request or via the Aladdin website.

For bulk quantities, custom packaging, or academic pricing inquiries, please contact Aladdin Scientific customer service. Orders can be placed online through the Aladdin Scientific catalog portal. Standard shipping conditions apply; expedited cold-chain shipping is available on request.

Cross-reference: This product is also cataloged under the reference code HY-P0125B (MCE-TJY).

Frequently asked questions

What is the difference between Elamipretide and Elamipretide triacetate?

Elamipretide and Elamipretide triacetate refer to the same active tetrapeptide but in different salt forms. In the triacetate salt, three acetate anions serve as counterions to the peptide's cationic residues. This salt form generally offers improved powder stability and hygroscopicity characteristics compared with the trifluoroacetate (TFA) salt, and it is preferred for biological studies because acetate is physiologically compatible. The biological activity of the peptide itself is equivalent between salt forms once dissolved.

What are the recommended storage conditions for Elamipretide triacetate (SKU E1439311)?

The lyophilized powder should be stored at −20 °C, away from light and moisture. Reconstituted stock solutions should be aliquoted to avoid repeated freeze-thaw cycles and stored at −80 °C for short-term use. Always refer to the lot-specific certificate of analysis (CoA) for definitive storage guidance, as conditions may be updated.

How does Elamipretide triacetate accumulate in mitochondria without relying on membrane potential?

Unlike triphenylphosphonium (TPP)-conjugated compounds that rely on the large negative mitochondrial membrane potential (ΔΨm) for electrophoretic uptake, Elamipretide concentrates in the inner mitochondrial membrane through direct electrostatic and hydrophobic interactions with cardiolipin. Because cardiolipin is almost exclusively located in the IMM, this lipid-mediated targeting is independent of ΔΨm, allowing the peptide to reach and protect even severely depolarized or damaged mitochondria.

Is Elamipretide triacetate suitable for in vivo animal studies?

Elamipretide triacetate has been used extensively in preclinical rodent models via subcutaneous, intravenous, and intraperitoneal routes. The triacetate salt form and aqueous solubility make it compatible with parenteral formulations. Researchers should determine appropriate dosing, route, and vehicle empirically for their specific model; published literature provides reference dosing frameworks, though these should be validated internally.

What analytical methods are used to confirm the identity and purity of Elamipretide triacetate?

Purity is typically assessed by reverse-phase high-performance liquid chromatography (RP-HPLC), and molecular identity is confirmed by mass spectrometry (MS), usually ESI-MS or MALDI-TOF. The certificate of analysis (CoA) for each lot of SKU E1439311 provides the specific purity percentage and analytical data. Researchers requiring additional characterization (e.g., NMR) should contact Aladdin Scientific customer service.

References

1. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology. 2014;171(8):2029-2050. doi:10.1111/bph.12461
2. Birk AV, Liu S, Soong Y, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology. 2013;24(8):1250-1261. doi:10.1681/ASN.2012121216
3. Zhao K, Zhao GM, Wu D, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. Journal of Biological Chemistry. 2004;279(33):34682-34690. doi:10.1074/jbc.M402999200
4. Daubert MA, Yow E, Dunn G, et al. Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. JACC: Heart Failure. 2017;5(8):609-618. doi:10.1016/j.jchf.2017.04.007

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.