SS-31 (Elamipretide)

Overview

SS-31, also known as Elamipretide, is a synthetic, cell-permeable tetrapeptide C32H49N9O5 engineered for precise mitochondrial targeting. It is distinguished by its ability to cross cell membranes and localize within the inner mitochondrial membrane (IMM) without the need for a mitochondrial membrane potential.

In molecular research, SS-31 is primarily investigated for its high-affinity binding to cardiolipin, a unique phospholipid critical for mitochondrial structure. By stabilizing cardiolipin-rich membranes, researchers use SS-31 to study the preservation of mitochondrial cristae, the optimization of electron transport chain (ETC) efficiency, and the reduction of reactive oxygen species (ROS). It serves as a vital tool for understanding energy metabolism and cellular resilience in models of aging and metabolic stress.

Key Research Applications

SS-31 has undergone significant scrutiny in Phase 2/3 clinical trials and remains a primary compound for investigating:

• Mitochondrial Bioenergetics: Research into ATP synthesis, oxygen consumption rates, and the regulation of mitochondrial respiration.
• Cardiolipin Dynamics: Modeling the stabilization of mitochondrial cristae and membrane integrity through peptide–lipid interactions.
• Oxidative Stress & ROS: Investigating the reduction of oxidative damage and the modulation of reactive oxygen species production.
• Organ-Specific Models: Experimental research into heart failure, ischemia-reperfusion injury, and Barth syndrome.
• Neurodegeneration: Studies focusing on age-related mitochondrial decline and its role in neurodegenerative disease models.

Additional Details

• Synonyms: Elamipretide, MTP-131, Bendavia
• Sequence: D-Arg-Dmt-Lys-Phe-NH₂

Handling & Reconstitution

Due to its cationic nature and sensitivity, SS-31 requires meticulous handling:

• Reconstitution: Use sterile water or an appropriate buffered aqueous solution.
• Technique: This peptide is hygroscopic; handle under dry conditions. Gently swirl until fully dissolved and avoid vigorous shaking to maintain structural stability.
• Stability: Immediately aliquot reconstituted solutions to minimize freeze-thaw cycles. Store at –20°C or below for long-term stability.
• Assay Considerations: Note that salt forms (e.g., acetate or TFA) may affect solubility and handling characteristics in sensitive in-vitro assays.

Important Safety Information

For Research Use Only. This product is intended strictly for laboratory and in-vitro research. Although it has been studied in clinical trials for various mitochondrial and cardiac indications, it is not for human or veterinary use, nor is it intended for diagnostic or therapeutic applications. Researchers must utilize appropriate controls to interpret data accurately across different cell types and experimental environments.

References

• Birk, A. V., et al. (2013). Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Journal of Biological Chemistry, 288(33), 24113-24126. PubMed
• Chavez, J. D., et al. (2020). Mitochondrial protein interaction landscape of SS-31. Proceedings of the National Academy of Sciences, 117(27), 15514-15523. PNAS
• Stealth BioTherapeutics. (2024). Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial. Journal of Neuromuscular Diseases / PubMed. PubMed
• Szeto, H. H., & Schiller, P. W. (2008). Novel therapies targeting inner mitochondrial membrane—from discovery to clinical development. Pharmaceutical Research, 25(9), 2123-2131. PubMed
• Tung, J., et al. (2025). Cardiolipin remodelling in mitochondrial therapeutics: translational evidence chains from elamipretide to emerging strategies. Frontiers in Physiology, 16, Article 1813119. Frontiers