SS-31 10mg

Introduction to SS-31 Peptide

SS-31, also known as Elamipretide, Bendavia, or MTP-131, is a synthetic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) designed for laboratory research to target and stabilize mitochondria, the cellular powerhouses critical for energy production and homeostasis. With a molecular weight of 639.8 g/mol and a net charge of +3 at physiological pH, SS-31 is a cell-permeable, aromatic-cationic peptide that selectively accumulates in the inner mitochondrial membrane (IMM) via electrostatic and hydrophobic interactions with cardiolipin (CL), a phospholipid essential for mitochondrial function. This unique targeting capability allows SS-31 to modulate oxidative stress and bioenergetics, making it a promising tool for preclinical studies of mitochondrial dysfunction-related conditions. Unlike traditional antioxidants, SS-31’s mechanism involves stabilizing mitochondrial structure and function rather than directly scavenging reactive oxygen species (ROS). This SEO-optimized article provides a comprehensive overview of SS-31’s chemical properties, mechanisms of action, preclinical research applications, and limitations, adhering to U.S. Food and Drug Administration (FDA) regulations by restricting its scope to laboratory research and explicitly avoiding endorsement for human use.

Chemical and Structural Properties

SS-31’s design as a Szeto-Schiller (SS) peptide optimizes its mitochondrial specificity and stability. Its sequence, incorporating dimethyltyrosine (Dmt), enhances its ability to penetrate cell and organelle membranes, localizing to the IMM where cardiolipin is abundant. The peptide’s positive charge facilitates electrostatic interactions with the negatively charged cardiolipin, while its hydrophobic residues ensure stable binding. SS-31 is water-soluble and lyophilized for long-term storage at -20°C, maintaining bioactivity in experimental protocols. Its small size and lack of effect on healthy mitochondria make it ideal for studying pathological conditions without perturbing normal cellular function. Key properties include:

• Tetrapeptide with sequence D-Arg-Dmt-Lys-Phe-NH2.

• Molecular weight of 639.8 g/mol; net charge +3 at physiological pH.

• Lyophilized for stability at -20°C or lower.

• Selectively targets cardiolipin in the IMM via electrostatic/hydrophobic interactions.

Mechanisms of Action

SS-31’s efficacy in preclinical research arises from its ability to stabilize mitochondrial structure and function, primarily through interactions with cardiolipin. By binding to cardiolipin, SS-31 prevents its peroxidation, maintains cristae architecture, and enhances electron transport chain (ETC) efficiency, reducing ROS production and promoting ATP synthesis. Preclinical studies in rodent and cellular models have elucidated its protective effects against oxidative stress and mitochondrial dysfunction. Primary mechanisms include:

• Cardiolipin Stabilization: Binds cardiolipin to prevent peroxidation, preserving ETC function. A 2013 study in Journal of the American Society of Nephrology showed SS-31 re-energized ischemic mitochondria in rats (Birk et al., 2013).

• ROS Reduction: Inhibits cytochrome c peroxidase activity, reducing mitochondrial ROS without direct scavenging.

• ATP Synthesis Enhancement: Improves electron flux through ETC complexes I and IV, increasing ATP output, as demonstrated in aged mouse muscle (Campbell et al., 2019).

• Anti-Inflammatory Effects: Suppresses pro-inflammatory cytokine production, supporting tissue repair. A 2019 Journal of Neuroinflammation study reported reduced inflammation in LPS-treated mice (Zhao et al., 2019).

• Anti-Apoptotic Properties: Prevents mitochondrial permeability transition pore (mPTP) opening, reducing cytochrome c release and apoptosis.

These mechanisms position SS-31 as a versatile tool for mitochondrial research.

Preclinical Research Applications

SS-31’s ability to target mitochondrial dysfunction makes it a valuable peptide for preclinical studies across multiple organ systems. Its protective effects have been validated in animal models (e.g., mice, rats) and cellular assays, particularly in conditions characterized by oxidative stress and impaired bioenergetics.

Key applications include:

• Neurodegenerative Disorders: Protected neurons in models of Alzheimer’s and Parkinson’s by reducing oxidative stress and preserving mitochondrial function (Manczak et al., 2010).

• Cardiovascular Diseases: Improved left ventricular function in heart failure models and reduced ischemia-reperfusion injury in rats (Brown et al., 2014).

• Renal Diseases: Ameliorated glomerulosclerosis and restored ATP production in aged mice and ischemia-reperfusion models (Sweetwyne et al., 2017; Szeto et al., 2011).

• Atherosclerosis: Reduced plaque formation and oxidative stress in ApoE-/- mice fed a Western diet (Li et al., 2017).

• Friedreich Ataxia: Upregulated frataxin expression and improved mitochondrial quality in patient-derived cells (Zhao et al., 2017).

• Skeletal Muscle Dysfunction: Enhanced exercise tolerance in aged mice by improving mitochondrial respiration (Campbell et al., 2019).

• Ophthalmic Disorders: Mitigated retinal damage in models of age-related macular degeneration (AMD) and glaucoma (Szeto, 2006).

SS-31’s specificity for dysfunctional mitochondria enhances its utility in targeted research.

Research Considerations and Limitations

Preclinical research with SS-31 requires careful consideration of scientific, regulatory, and ethical factors to ensure valid results. Its limited study in certain models and mechanisms necessitates further exploration.
Key considerations include:

• Regulatory Compliance: Not FDA-approved for human use; restricted to laboratory research. FDA warns against marketing for human consumption as unapproved drugs.

• Limited Renal Research: Few studies on renal diseases, with gaps in understanding mitophagy effects (Zhu et al., 2022).

• Dosing Protocols: Subcutaneous doses (1–3 mg/kg in mice) require model-specific calibration for optimal pharmacokinetics.

• Side Effects: Mild injection-site irritation in animal models; long-term effects beyond 8 weeks understudied.

• Delivery Systems: May require advanced carriers (e.g., nanoparticles) for enhanced tissue repair applications.

• Ethical Standards: Requires IACUC approvals to ensure animal welfare and distress minimization.

• Study Design: Robust controls and standardized protocols are critical to address model variability.

These factors promote rigorous and ethical research practices.

Future Research Directions
SS-31’s mitochondrial specificity offers significant potential for advancing preclinical research. Its ability to target cardiolipin and modulate bioenergetics suggests opportunities for innovative applications in mitochondrial therapeutics.
Potential directions include:

• Novel Derivatives: Develop SS-31 analogs with enhanced cardiolipin affinity or stability (Zhao et al., 2023).

• Delivery Optimization: Explore nanoparticles or hydrogels for targeted delivery in tissue repair studies.

• Mechanistic Studies: Investigate mitophagy and protein interactions using omics technologies.

• Expanded Models: Study effects in chronic disease models like diabetic nephropathy or neurodegenerative progression.

• Combination Therapies: Test synergies with other mitochondrial-targeted agents or peptides.

These directions position SS-31 as a cornerstone for future mitochondrial research.

Conclusion

SS-31, a mitochondria-targeting tetrapeptide, is a transformative tool for preclinical research in mitochondrial dysfunction and tissue repair. Its ability to stabilize cardiolipin, reduce ROS, enhance ATP synthesis, and suppress inflammation enables studies in neurodegenerative disorders, cardiovascular diseases, renal dysfunction, and beyond. With a stable pharmacokinetic profile and specificity for dysfunctional mitochondria, SS-31 supports robust experimental protocols. By adhering to FDA regulations and ethical standards, researchers can harness SS-31 to uncover new insights into mitochondrial biology, advancing peptide research and biomedical science.

Citations

1. Birk, A. V., et al. (2013). The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology, 24(8), 1250–1261. https://pubmed.ncbi.nlm.nih.gov/23687361/

2. Brown, D. A., et al. (2014). Reduction of early reperfusion injury with the mitochondria-targeting peptide Bendavia. Journal of Cardiovascular Pharmacology, 19(1), 121–132. https://pubmed.ncbi.nlm.nih.gov/24145016/

3. Campbell, M. D., et al. (2019). Improving mitochondrial function with SS-31 reverses age-related redox stress. Free Radical Biology and Medicine, 134, 268–281. https://pubmed.ncbi.nlm.nih.gov/30639781/

4. Manczak, M., et al. (2010). Mitochondria-targeted antioxidants protect against amyloid-beta toxicity. Journal of Alzheimer’s Disease, 20(Suppl 2), S609–S631. https://pubmed.ncbi.nlm.nih.gov/20442426/

5. Szeto, H. H. (2006). Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS Journal, 8(3), E521–E531. https://pubmed.ncbi.nlm.nih.gov/17025265/

6. Szeto, H. H., et al. (2011). Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury. Journal of the American Society of Nephrology, 22(6), 1041–1052. https://pubmed.ncbi.nlm.nih.gov/21546574/

7. Sweetwyne, M. T., et al. (2017). The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age. Kidney International, 91(5), 1126–1145. https://pubmed.ncbi.nlm.nih.gov/28063595/

8. Li, J., et al. (2017). Chronic administration of SS-31 prevents atherosclerotic development in ApoE knockout mice. PLOS ONE, 12(9), e0184738. https://pubmed.ncbi.nlm.nih.gov/28957384/

9. Zhao, W., et al. (2017). Peptide SS-31 upregulates frataxin expression and improves mitochondrial quality in Friedreich ataxia. Scientific Reports, 7(1), 9840. https://pubmed.ncbi.nlm.nih.gov/28851934/

10. Zhao, W., et al. (2019). Elamipretide (SS-31) improves mitochondrial dysfunction in LPS-treated mice. Journal of Neuroinflammation, 16(1), 234. https://pubmed.ncbi.nlm.nih.gov/31752924/

11. Zhu, J., et al. (2022). SS-31, a mitochondria-targeting peptide, ameliorates kidney disease. Oxidative Medicine and Cellular Longevity, 2022, 2588883. https://pubmed.ncbi.nlm.nih.gov/35656027/

12. Zhao, W., et al. (2023). Discovery of novel SS-31 derivatives as potent agents to ameliorate inflammation. RSC Advances, 13(28), 19367–19378. https://pubmed.ncbi.nlm.nih.gov/37424912/[](https://pubs.rsc.org/en/content/articlehtml/2024/ra/d4ra05517a)

FDA Disclaimer
This article is for research and educational purposes only. SS-31 is not approved by the U.S. Food and Drug Administration (FDA) for human use or consumption. It is intended solely for laboratory research. Consult qualified professionals and adhere to regulatory guidelines when handling research peptides.