SS-31

SS-31 Peptide - 10mg Overview

SS-31 Peptide (also known as Elamipretide) is a first-in-class, mitochondria-targeted tetrapeptide. It is uniquely capable of crossing the plasma membrane and localizing within the inner mitochondrial membrane without relying on a membrane potential. The primary mechanism of action involves a high-affinity interaction with cardiolipin, a phospholipid that is vital for the structure of mitochondrial cristae and the organization of the electron transport chain. By stabilizing cardiolipin, SS-31 prevents the formation of excessive reactive oxygen species and promotes efficient energy production. This makes it a significant subject of study for conditions characterized by bioenergetic failure and oxidative damage.

SS-31 Peptide Structure

The structural integrity of SS-31 allows for rapid uptake into the mitochondria across diverse cell types.

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

Specification Category

Technical Detail

Systematic Name

Elamipretide

Molecular Formula

C32H49N9O5

Sequence Breakdown

D-Arg-Dmt-Lys-Phe-NH2

Molecular Mass

639.8 grams per mole

Solubility Profile

Highly water soluble

Appearance

Lyophilized crystalline powder

SS-31 Peptide Research

Mitochondria Improvement

The research surrounding SS-31 focuses heavily on its ability to restore mitochondrial bioenergetics. In cases of Primary Mitochondrial Diseases (PMDs), the body's ability to synthesize adenosine triphosphate (ATP) is severely compromised. Scientific studies in animal models have shown that SS-31 can reverse these deficits by optimizing the electron transport chain. For example, in rats with ischemic injury, SS-31 accelerated the recovery of ATP levels and protected the physical structure of the kidneys. While human phase 3 trials required more specific measurement benchmarks, the phase 2 trials confirmed that SS-31 could improve exercise capacity and physical performance in subjects with mitochondrial myopathy.

Ischemia

SS-31 has shown promise in treating heart failure and ischemic events. In human cardiac tissue, the peptide has been observed to improve mitochondrial oxygen flux. This is particularly important because heart failure often triggers a cycle where damaged mitochondria lead to further cardiac decline. Chronic treatment in canine models of advanced heart failure resulted in improved left ventricular function and reduced cardiac remodeling. In acute settings, such as myocardial infarction, SS-31 helps preserve heart muscle by reducing biomarkers of cell death.

Diabetes

Metabolic health research has utilized SS-31 to investigate the link between mitochondrial dysfunction and type 2 diabetes. Studies suggest the peptide reduces oxidative stress in small blood vessels, which could potentially slow the progression of microvascular complications. Furthermore, SS-31 increases levels of SIRT1, a protein that enhances insulin sensitivity and lowers systemic inflammation.

Reduces Inflammation

The anti-inflammatory properties of SS-31 are a key area of current research. By downregulating the FIS1 protein, the peptide helps maintain proper mitochondrial division and reduces the inflammatory signals associated with mitochondrial fragmentation. It also inhibits NF-kappaB signaling, a major pathway for chronic cellular inflammation.

SS-31 Summary

SS-31 is a versatile research tool for exploring the restoration of cellular energy and the mitigation of oxidative stress. While it was initially developed for rare mitochondrial diseases, its ability to stabilize cardiolipin suggests broad applications in cardiology, neurology, and metabolic science.

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.

STORAGE

Storage Instructions

Peptides are delivered in a lyophilized (freeze-dried) state, ensuring stability during transit for several months. Upon arrival, the product should be kept in a controlled environment. Once reconstituted with bacteriostatic water, the solution remains stable for approximately 30 days if stored in a refrigerator.

Best Practices For Storing Peptides

Maintaining a cold, dark environment is essential for preserving peptide quality. For immediate use, refrigeration below 4 degrees Celsius is sufficient. For long-term storage, a freezer reaching minus 80 degrees Celsius is recommended to prevent the degradation of the amino acid chain.

Preventing Oxidation and Moisture Contamination

Condensation can damage lyophilized powder. Always allow the vial to reach room temperature before breaking the seal. Minimize exposure to air to prevent oxidation, particularly for peptides containing sensitive amino acids.

Storing Peptides In Solution

Peptide solutions have a limited shelf life. If the peptide is in solution, it should be divided into aliquots and kept frozen to avoid repeated freeze-thaw cycles, which can break the peptide bonds.

Peptide Storage Containers

Borosilicate glass vials are recommended for their chemical stability and resistance to temperature changes. Polypropylene plastic vials are also suitable for research purposes and reduce the risk of breakage.

Peptide Storage Guidelines: General Tips

• Maintain storage in a cold and dark location.
• Keep the peptide in powder form until ready for use.
• Prevent air and moisture exposure.
• Use smaller aliquots to avoid thawing the entire supply.
• Do not use frost-free freezers for long-term storage.