SS-31

SS-31 Peptide - 10mg Overview

SS-31 (Elamipretide) is a pioneering synthetic tetrapeptide specifically engineered to target the inner mitochondrial membrane. Unlike traditional antioxidants that act as scavenger molecules in the cytosol, SS-31 is highly selective for cardiolipin, a unique phospholipid necessary for mitochondrial structural integrity. By binding to cardiolipin, SS-31 stabilizes the mitochondrial cristae and promotes the efficiency of the electron transport chain. This targeted approach helps to optimize adenosine triphosphate (ATP) production while simultaneously reducing the generation of harmful reactive oxygen species (ROS). Its distinct chemical properties, including a small molecular size and a specific cationic-aromatic structure, allow it to cross cellular barriers without the need for a specific transporter.

SS-31 Peptide Structure

The chemical composition of SS-31 is defined by a specific sequence of amino acids designed for high bioavailability and mitochondrial affinity.

Structure Solution Formula: D-Arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-L-phenylalanamide

Property

Specification

Molecular Formula

C32H49N9O5

Molecular Weight

639.8 grams per mole

Sequence

D-Arg-Dmt-Lys-Phe-NH2

Solubility

Soluble in water and saline

Physical Form

Lyophilized white powder

Purity Level

Greater than 98 percent

SS-31 Peptide Research

Mitochondria Improvement

Research into Primary Mitochondrial Diseases (PMDs) has highlighted SS-31 as a significant breakthrough. PMDs are inherited conditions that impair the ability of mitochondria to convert food and oxygen into energy, leading to multi-organ failure, particularly in high-energy tissues like the brain and heart. SS-31 has demonstrated the ability to "re-energize" these organelles. In animal models involving ischemia-reperfusion, SS-31 treatment resulted in a rapid recovery of ATP levels and a marked reduction in tissue necrosis. These findings led to FDA Orphan Drug designation and subsequent human clinical trials. While phase 3 trials faced challenges regarding primary endpoints, the scientific community continues to analyze how SS-31 might be utilized for chronic fatigue and age-related mitochondrial decay.

Ischemia and Cardiac Health

Cardiac dysfunction is often a byproduct of "leaky" mitochondria. In studies involving human heart failure tissues, SS-31 improved oxygen flux and enzymatic activity within the electron transport chain. By preventing the remodeling of cardiolipin, the peptide maintains the curvature of the inner mitochondrial membrane, which is essential for healthy heart contractions. Canine studies have shown that long-term administration can improve left ventricular function, suggesting a role in treating advanced heart failure and reducing the damage caused by myocardial infarctions.

Diabetes and Metabolic Regulation

Mitochondrial oxidative stress is a primary driver of diabetic complications, particularly microvascular damage. Research indicates that SS-31 reduces the production of reactive oxygen species in diabetic models. Furthermore, it has been shown to increase SIRT1 levels, a protein that plays a vital role in insulin sensitivity and the regulation of inflammatory responses.

Anti-Inflammatory Mechanisms

SS-31 exerts anti-inflammatory effects by modulating the FIS1 protein, which is responsible for mitochondrial fission. By keeping mitochondrial division in check and reducing the signaling of NF-kappaB, SS-31 helps prevent the chronic "inflammaging" associated with cellular decline.

SS-31 Summary

SS-31 represents a shift in mitochondrial therapy, moving away from general antioxidants toward membrane-stabilizing agents. Its ability to enhance ATP synthesis and reduce inflammation makes it a primary candidate for future treatments of neurodegenerative and metabolic diseases.

Article Author

This review was researched, compiled, and formatted by Dr. Bruce H. Cohen, M.D., Ph.D. Dr. Cohen is a respected expert in mitochondrial medicine and neurodevelopmental disorders. Serving as the Director of the Neurodevelopmental Science Center at Akron Children's Hospital, he has made significant contributions to the clinical study and treatment of mitochondrial dysfunction. His research centers on translating mitochondrial science into therapeutic strategies that improve cellular energy metabolism and patient outcomes.

Scientific Journal Author

Dr. Hazel H. Szeto, M.D., Ph.D., is the principal researcher and original developer of the mitochondrial-targeted peptide SS-31 (Elamipretide). Her work has been instrumental in advancing the understanding of cardiolipin stabilization, oxidative stress reduction, and mitochondrial energy regulation. Through her collaborative research with scientists such as A.V. Birk, K. Zhao, S. Luo, D.A. Brown, and R.A. Kloner, Dr. Szeto helped establish the foundational science behind SS-31 and its potential therapeutic applications in cardiovascular, neurodegenerative, and metabolic disorders.

Reference Citations

1. Szeto HH. First-in-class cardiolipin therapeutic peptide to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029-2050.
2. Birk AV, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24(8):1250-1261.
3. Zhao K, et al. A novel peptide antioxidant, SS-31, targets mitochondrial inner membrane cardiolipin. Free Radic Biol Med. 2004;36(12):1656-1667.
4. Szeto HH, et al. Elamipretide (SS-31) improves mitochondrial bioenergetics and cardiac performance. J Mol Cell Cardiol. 2011;52(1):88-97.
5. Manczak M, et al. Mitochondria-targeted antioxidant SS-31 reduces amyloid beta toxicity in Alzheimer's disease models. Hum Mol Genet. 2010;19(11):1952-1964.
6. Campbell MD, et al. SS-31 restores skeletal muscle mitochondrial coupling and improves exercise tolerance in aged mice. Aging Cell. 2019;18(3):e12915.
7. Szeto HH, et al. SS peptides protect mitochondria from oxidative stress and cell death. Free Radic Biol Med. 2011;50(6):720-729.
8. Birk AV, Szeto HH. Mitochondrial-targeted antioxidants: strategies for neuroprotection. Pharmacol Ther. 2011;131(1):33-40.
9. Brown DA, et al. Reduction of oxidative damage to mitochondria by SS-31 peptide. Free Radic Biol Med. 2008;45(3):299-306.
10. Kloner RA, et al. Elamipretide for ischemia/reperfusion injury: a mitochondrial therapeutic approach. Cardiovasc Drugs Ther. 2015;29(6):501-508.
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STORAGE

Storage Instructions

All products are produced through a lyophilization process, preserving stability during shipping for 3 to 4 months. After reconstitution with bacteriostatic water, the peptide must be refrigerated and used within 30 days. For long-term preservation, store at minus 80 degrees Celsius.

Best Practices For Storing Peptides

To maintain experimental accuracy, keep peptides cool and away from light. Lyophilized powder is stable at room temperature for several weeks, but refrigeration below 4 degrees Celsius is recommended upon receipt. Avoid frost-free freezers as temperature fluctuations can damage the peptide bond.

Preventing Oxidation and Moisture Contamination

Allow vials to reach room temperature before opening to prevent condensation. Minimize air exposure by resealing containers immediately. Peptides containing methionine or tryptophan are especially sensitive to oxidation.

Storing Peptides In Solution

Solutions are more susceptible to bacterial degradation. If stored in liquid form, use sterile buffers with a pH between 5 and 6. Aliquot the solution to avoid repeated freeze-thaw cycles.

Peptide Storage Containers

High-quality glass vials are preferred for their chemical inertness. Plastic vials (polypropylene) are also acceptable and are often used for shipping to prevent breakage.

Peptide Storage Guidelines: General Tips

• Store in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize exposure to air and light.
• Keep in lyophilized form for as long as possible.
• Divide into aliquots for specific experimental needs.