SS-31 (Elamipretide) Peptide 10mg – Mitochondria-Targeted Tetrapeptide

Chemical diagram for SS-31 (Elamipretide) source: https://en.wikipedia.org/wiki/Elamipretide#/media/File:Elamipretide_structure.svg

KEY SPECIFICATIONS:

PRODUCT OVERVIEW:

SS-31, also known as Elamipretide, is a mitochondria-targeted synthetic tetrapeptide designed to selectively interact with the inner mitochondrial membrane. Specifically, this peptide demonstrates remarkable selectivity for cardiolipin—a unique phospholipid found exclusively in mitochondria. Consequently, SS-31 stabilizes membrane architecture and optimizes bioenergetics in research models.

Research demonstrates that SS-31 accumulates in mitochondria independently of membrane potential. Furthermore, it binds cardiolipin through dual mechanisms: hydrophobic interactions via dimethyl-tyrosine and phenylalanine residues, and electrostatic attractions via positively charged D-arginine and lysine. As a result, this binding stabilizes cardiolipin against peroxidation, preserves cristae integrity, and enhances electron transport chain efficiency. BIONIX supplies SS-31 with ≥99% HPLC-verified purity for mitochondrial research.

MECHANISM OF ACTION:

SS-31 operates through highly specific cardiolipin binding, enabling mitochondrial protection and bioenergetic optimization.

Structural Design Features

SS-31’s unique structure enables selective mitochondrial targeting through the aromatic-cationic motif:

Szeto-Schiller Peptide Class: SS-31 belongs to this peptide family characterized by alternating aromatic-cationic motifs. Consequently, this structure enables both cell membrane penetration and selective mitochondrial accumulation.

Cardiolipin Binding Mechanism

Cardiolipin is a distinctive phospholipid with critical roles in mitochondrial function. Specifically, it contains four fatty acid chains and two phosphate groups, making it essential for ETC complex assembly and cristae structure. However, cardiolipin is highly susceptible to oxidation and experiences compositional alterations with age.

SS-31 interacts with cardiolipin through complementary binding:

Consequently, this dual binding mode positions SS-31 at the membrane surface where it prevents cardiolipin peroxidation, maintains cristae architecture, stabilizes respiratory supercomplexes, and modulates cytochrome c interactions.

ETC Component Effects

SS-31’s cardiolipin stabilization directly affects oxidative phosphorylation:

Furthermore, by organizing ETC supercomplexes, SS-31 promotes efficient oxidative phosphorylation. As a result, research models demonstrate increased oxygen consumption, enhanced ATP production, and reduced reactive oxygen species generation.

ROS Reduction Mechanisms

SS-31 reduces oxidative stress through multiple pathways:

Therefore, the combination of structural stabilization and direct antioxidant activity contributes to SS-31’s protective effects in oxidative stress models.

RESEARCH APPLICATIONS:

Mitochondrial Dysfunction Models

SS-31 enables investigation of electron transport chain disorders. Specifically, researchers examine:

• Experimental Parameters: Oxygen consumption rate (OCR via Seahorse XF), ATP production (luciferase/HPLC), membrane potential (JC-1, TMRM), ROS production (MitoSOX, DCF-DA), supercomplex assembly (BN-PAGE), cardiolipin content (NAO staining, LC-MS)
• Research Questions: How does cardiolipin stabilization affect ETC efficiency? Can SS-31 rescue bioenergetic deficits? What is the relationship between supercomplex stability and ROS?

Ischemia-Reperfusion Research

SS-31 is extensively studied in ischemia-reperfusion injury models. Consequently, applications include:

• Cardiac Models: Isolated heart perfusion (Langendorff), in vivo coronary artery occlusion, cardiomyocyte hypoxia-reoxygenation, myocardial infarction size quantification
• Other Organ Models: Renal, hepatic, cerebral, and limb ischemia studies
• Measured Endpoints: Infarct size reduction, functional recovery, mitochondrial swelling prevention, cristae preservation (electron microscopy), apoptosis markers

Cardioprotection Studies

Cardiac applications represent a major research focus. Specifically:

• Protective Mechanisms: Mitochondrial permeability transition pore (mPTP) inhibition, cytochrome c release prevention, cardiolipin preservation during stress, energy metabolism maintenance
• Disease Models: Heart failure, pressure overload hypertrophy, doxorubicin cardiotoxicity, diabetic cardiomyopathy

Neurodegenerative Research

SS-31’s mitochondrial effects are investigated in neurodegeneration models. Furthermore:

• Research Areas: Alzheimer’s disease (mitochondrial dysfunction component), Parkinson’s disease (Complex I deficiency), optic neuropathy (Leber’s hereditary), age-related cognitive decline
• Neuronal Endpoints: Synaptic mitochondrial function, axonal transport, neuronal survival markers, cognitive function testing

Oxidative Stress Research

SS-31 enables investigation of ROS-mediated pathology. Consequently:

• Oxidative Stress Models: Chemical pro-oxidant exposure (paraquat, H₂O₂), hyperoxia models, aging-associated oxidative damage, metabolic stress (high glucose, lipotoxicity)
• Measured Parameters: Lipid peroxidation (MDA, 4-HNE), protein oxidation (carbonyl content), DNA damage (8-OHdG), antioxidant enzyme activity

Aging and Longevity Research

SS-31 is investigated in mitochondrial aging contexts. Specifically:

• Age-Related Changes: Declining mitochondrial function, increased ROS production, cardiolipin composition alterations, reduced ATP production capacity
• Research Applications: Aged tissue bioenergetics, exercise capacity in aging, sarcopenia models, healthspan extension studies

However, all applications remain strictly limited to controlled laboratory research environments.

ANALYTICAL VERIFICATION:

BIONIX SS-31 undergoes comprehensive analytical characterization:

• HPLC Analysis: ≥99% purity via reversed-phase chromatography, separating components based on chemical interactions
• Mass Spectrometry: Exact molecular weight confirmation (639.8 g/mol) and sequence verification including D-Arg configuration and dimethyltyrosine modification
• D-Arginine Verification: Stereochemistry confirmation for peptidase resistance
• Additional Parameters: Amino acid composition, residual solvent testing, peptide content, endotoxin testing (LAL)

Physical Characteristics:

DEVELOPMENT STATUS:

SS-31 represents an advanced mitochondrial-targeted research compound:

• Discovery: Szeto-Schiller peptide class (aromatic-cationic motif design)
• Clinical Trials: Completed Phase 2/3 as Elamipretide for specific indications
• Clinical Status: Research compound for broader applications; not approved for general therapeutic use
• Mechanism: Well-characterized cardiolipin binding and ETC stabilization
• Regulatory Note: Research compound status for laboratory investigation
• Availability: BIONIX supplies exclusively for controlled laboratory research
• Distinction: Only phospholipid-targeting peptide with cardiolipin specificity

Unlike other mitochondrial modulators with broader targets, SS-31 demonstrates precise cardiolipin selectivity. Consequently, researchers gain a unique tool for investigating inner mitochondrial membrane dynamics.

FREQUENTLY ENCOUNTERED INQUIRIES:

What distinguishes SS-31 from other mitochondrial peptides? SS-31 is distinguished by specific binding to cardiolipin, a phospholipid found exclusively in the inner mitochondrial membrane. Unlike other mitochondrial modulators with broader targets, this selectivity enables precise investigation of mitochondrial bioenergetics. Specifically, binding occurs through complementary electrostatic (D-Arg, Lys to phosphate groups) and hydrophobic (dimethylTyr, Phe to fatty acid chains) interactions. Therefore, SS-31 provides targeted ETC research capabilities.

How should SS-31 be reconstituted for research? Reconstitute with sterile distilled water or appropriate buffer according to experimental protocols. Specifically, allow the vial to reach room temperature before opening, add solvent gently along the vial wall, and swirl until dissolved—avoid vortexing. Furthermore, aliquot immediately to prevent repeated freeze-thaw cycles. Consequently, proper handling maintains peptide integrity for consistent experimental results.

What quality control does BIONIX perform? Each batch undergoes HPLC testing for ≥99% purity and mass spectrometry verification for molecular identity. Specifically, this includes confirmation of D-arginine stereochemistry and dimethyltyrosine modification. Furthermore, batch-specific Certificates of Analysis document amino acid composition and all quality parameters. Therefore, researchers receive analytically verified material.

Is SS-31 stable at room temperature? Lyophilized SS-31 is optimally stable at -20°C. However, short-term storage at room temperature during shipping is acceptable. Consequently, long-term storage requires freezer conditions. Furthermore, after reconstitution, store solutions at 2-8°C and use within 2-4 weeks, or prepare aliquots and freeze for extended storage.

How does SS-31 reduce ROS production? SS-31 reduces reactive oxygen species through four mechanisms: (1) stabilizing ETC supercomplexes to minimize electron leakage; (2) protecting cardiolipin from peroxidation to maintain membrane integrity; (3) providing direct radical scavenging via the dimethyltyrosine residue; and (4) inhibiting mitochondrial permeability transition pore opening. Consequently, this multi-pronged approach addresses both ROS sources and consequences in research models.

What is the clinical development status? SS-31 (Elamipretide) has completed Phase 2/3 clinical trials for specific indications. However, BIONIX SS-31 is supplied exclusively for laboratory research purposes—not for clinical or therapeutic applications. Furthermore, the research compound enables investigation of mitochondrial mechanisms beyond specific clinical indications. Therefore, researchers should strictly limit applications to controlled laboratory environments.

REFERENCES:

• Szeto HH., “First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics,” Br J Pharmacol, 2014.
• Birk AV et al., “The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin,” J Am Soc Nephrol, 2013.
• PNAS 2020 — “Mitochondrial protein interaction landscape of SS-31,” 117(26):15363-15373.
• Zhao K et al., “Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane,” J Biol Chem, 2004.
• PMC 2025 — “Elamipretide: Structure, Mechanism of Action and Therapeutic Applications.”
• Szeto HH, Birk AV., “Serendipity and the discovery of novel compounds that restore mitochondrial plasticity,” Clin Pharmacol Ther, 2014.