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SS-31 (Elamipretide) | CAS: 736992-21-5

CAS Number:
736992-21-5
Chemical Classification:
Research peptide

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SS-31 (Elamipretide) (CAS 736992-21-5) is a mitochondria-targeted tetrapeptide designed to associate with cardiolipin and modulate inner-membrane bioenergetics under oxidative stress. Cardiac, renal, and skeletal-muscle models each emphasize different facets of mitochondrial dysfunction, so the peptide's apparent efficacy can shift with the stressor—ischemia-reperfusion versus chronic ROS elevation, for example. Laboratories employ it in isolated mitochondria respiration assays, Langendorff-perfused heart preparations, and tubular-cell injury models with ATP-depletion readouts. Documented by COA, LC-MS, HPLC, and NMR; restricted to research environments.

CAS
736992-21-5
Molecular Formula
C32H49N9O5
Molecular Weight
639.8 g/mol
Purity
≥98%
Appearance
White lyophilized powder
Storage
Store at -20°C

Analytical Documentation

COA✓ Available
LC-MS✓ Available
HPLC✓ Available
NMR✓ Available

Research Inquiry

Overview

SS-31, also known as elamipretide or Bendavia, is a mitochondria-targeting tetrapeptide with sequence D-Arg-Dmt-Lys-Phe-NH2 designed to associate with cardiolipin in the inner mitochondrial membrane. By stabilizing cardiolipin and reducing reactive oxygen species production from electron transport chain dysfunction, SS-31 serves as a research tool in oxidative phosphorylation, ischemia-reperfusion, and mitochondrial myopathy model systems. The D-amino acids and 2,6-dimethyltyrosine residue confer protease resistance and membrane intercalation properties. SS-31 enables investigators to test whether cardiolipin stabilization independently modifies ATP output and apoptotic signaling in cell and organ research platforms. Supplied at ≥98% purity (C32H49N9O5; 639.8 g/mol), this material supports controlled laboratory investigation under research-use-only conditions.

Mechanism of Action

SS-31 binds cardiolipin on the inner mitochondrial membrane, stabilizing cristae structure and optimizing electron transfer between complexes I, III, and IV in research mitochondria. Reduced electron leak lowers superoxide generation at complex I and III sites in oxidative stress models. SS-31 improves ATP synthesis efficiency in permeabilized muscle fibers from research animals with mitochondrial dysfunction. Cytochrome c release and caspase activation are attenuated in cell apoptosis assays when cardiolipin peroxidation is limited by peptide presence. The mechanism is physicochemical membrane stabilization rather than GPCR activation.

Receptor Binding & Signaling

SS-31 targets cardiolipin phospholipid rather than a protein receptor. Minimal binding to unrelated GPCRs or ion channels occurs at mitochondrial research concentrations. Membrane insertion depends on mitochondrial membrane potential in some flux assays. Off-target plasma protein binding is low relative to mitochondrial accumulation in tissue uptake studies.

Research Applications

Mitochondrial respiration and Seahorse assays

Isolated mitochondria and intact cells in XF analyzers measure oxygen consumption rates after SS-31 addition under ADP-stimulated conditions. Rotenone and antimycin controls define complex contributions. SS-31 validates cardiolipin-targeted improvement of bioenergetic parameters in research mitochondria.

Ischemia-reperfusion organ models

Heart and kidney ex vivo perfusion systems apply SS-31 during reperfusion phases to quantify infarct size, ROS probes, and ATP recovery in controlled research protocols. Animal models of transient artery occlusion use peptide administration per approved IACUC designs. Research focuses on mitochondrial injury biochemistry.

Mitochondrial myopathy cell models

Patient-derived fibroblasts and cybrid cell lines carrying mitochondrial DNA mutations serve as platforms for SS-31 rescue of membrane potential and growth defects. Cardiolipin mass spec profiles correlate with peptide responsiveness. Studies advance rare disease mitochondrial research in vitro.

Aging and sarcopenia mitochondrial function

Aged rodent skeletal muscle fibers test whether SS-31 restores coupled respiration and reduces lipid peroxidation products in mitochondrial fractions. Paired with exercise or sedentary controls in research designs. Outcomes inform aging mitochondrial biology without therapeutic claims.

Molecular Information

Sequence & Chain Summary

D-Arg-Dmt-Lys-Phe-NH2 (D-amino acid tetrapeptide).

Modification Type

C-terminal amide; Dmt (2,6-dimethyltyrosine) at position 2.

Structural Notes

SS-31 is a cationic amphipathic peptide with mass 639.8 g/mol. D-amino acids confer protease resistance. RP-HPLC and MS verify purity. Dimethyltyrosine fluorescence properties occasionally exploited in membrane localization microscopy research. Batch-specific molecular characterization—including mass confirmation and purity profiling—is available through COA, LC-MS, HPLC, and NMR documentation supplied with SS-31 (Elamipretide).

Molecular Formula
C32H49N9O5
Molecular Weight
639.8 g/mol
Purity Specification
≥98%

Experimental Notes

Stability

Lyophilized SS-31 stable at −20°C. Reconstituted peptide stable short-term refrigerated; avoid repeated freeze-thaw. Light exposure may affect Dmt residue over prolonged periods; store vials capped and protected. Lyophilized SS-31 (Elamipretide) should be protected from repeated freeze-thaw cycles, moisture, and prolonged exposure to ambient light where applicable. Analytical integrity is best preserved when material is stored under the conditions specified on the certificate of analysis.

Storage Conditions

Store at -20°C. SS-31 (Elamipretide) is supplied as white lyophilized powder. For long-term archival storage in research inventories, maintain sealed containers with desiccant where recommended and document lot numbers for traceability across experimental runs.

Laboratory Handling

Reconstitute in sterile water. Use within validated stability window for respiration assays sensitive to peptide degradation. Keep mitochondria preparations on ice during SS-31 addition protocols. Reconstitute only with appropriate research-grade solvents compatible with your assay format. Allow vials to reach equilibrium before opening, work under clean bench conditions, and label all working solutions with concentration, date, and researcher ID per institutional SOPs.

Frequently Asked Questions

Research-focused answers about SS-31 (Elamipretide). For laboratory use only — not medical advice.

What is SS-31 (Elamipretide) used for in research?
SS-31 is for mitochondrial biology and oxidative stress research in cell, organ, and animal models. Not for human or veterinary treatment of mitochondrial or cardiovascular conditions.
How does SS-31 (Elamipretide) work biologically?
SS-31 stabilizes cardiolipin in the inner mitochondrial membrane, improving electron transport efficiency and reducing ROS production in research models of mitochondrial dysfunction.
What receptors does SS-31 (Elamipretide) interact with?
Primary target is cardiolipin phospholipid in mitochondrial membranes, not a protein GPCR. Off-target receptor interactions are negligible at standard research concentrations.
Is SS-31 (Elamipretide) stable at room temperature?
Lyophilized SS-31 stable at −20°C. Reconstituted peptide stable short-term refrigerated; avoid repeated freeze-thaw. Light exposure may affect Dmt residue over prolonged periods; store vials capped and protected. For short-term laboratory workflows, minimize time at room temperature and return unused material to recommended storage promptly. SS-31 (Elamipretide) is not formulated for ambient long-term storage.
What is the recommended storage condition for SS-31 (Elamipretide)?
Store at -20°C. Store lyophilized material in a dedicated −20°C freezer, protect from moisture ingress, and avoid repeated temperature cycling. Reconstituted solutions should be aliquoted and frozen if not used within the validated window of your internal stability study.