SS-31 Lyophilized Powder

Overview

SS-31 (CAS 845225-24-3; INN: elamipretide) is a synthetic aromatic-cationic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH₂, where Dmt represents 2′,6′-dimethyltyrosine — a non-natural amino acid that confers both structural rigidity and enhanced membrane affinity. The compound was designed by Hazel Szeto and Peter Schiller to exploit the strong electrostatic gradient across the inner mitochondrial membrane, enabling selective accumulation within the inner membrane at concentrations orders of magnitude above plasma levels without requiring active transport. This membrane-targeting strategy represents a rational approach to delivering antioxidant and bioenergetic effects directly to the primary site of mitochondrial ROS production and ATP synthesis.

The primary molecular target of SS-31 within the inner mitochondrial membrane is cardiolipin — a unique dimeric phospholipid found almost exclusively in this membrane that serves as a structural scaffold for the respiratory chain complexes and plays an essential role in maintaining cristae architecture. SS-31 binds cardiolipin with high affinity and stabilizes the interaction between cardiolipin and cytochrome c — a key junction in electron transport that is disrupted under oxidative stress conditions. By preserving this interaction, SS-31 maintains electron transport chain integrity, reduces electron leak and superoxide generation, and sustains ATP production efficiency under conditions of mitochondrial stress, ischemia, or aging-associated dysfunction.

Technical Specifications

Key Research Findings

Szeto’s 2014 review in British Journal of Pharmacology established the mechanistic framework for SS-31’s cardiolipin-targeting strategy and synthesized data from preclinical models of heart failure, renal ischemia-reperfusion injury, and neurodegenerative disease [1]. In cardiac ischemia-reperfusion models, SS-31 pretreatment significantly reduced infarct size, preserved mitochondrial membrane potential, and attenuated cardiomyocyte apoptosis — effects attributed to maintained cardiolipin–cytochrome c interactions that prevent cytochrome c release into the cytosol and downstream caspase activation. In chronic heart failure models, SS-31 administration reversed mitochondrial cristae remodeling, restored Complex I activity, and improved cardiac output independent of hemodynamic loading — supporting a direct mitochondrial bioenergetic mechanism rather than indirect hemodynamic effects.

Siegel et al. published in Aging Cell in 2013 demonstrated that SS-31 administration rapidly improved skeletal muscle mitochondrial energetics and physical performance in aged mice, with significant increases in ex vivo mitochondrial H₂O₂ scavenging, ATP production rates, and in vivo treadmill performance [2]. The rapidity of the observed effects — measurable within hours of a single dose — is consistent with a direct biophysical mechanism at the inner membrane rather than a transcriptional or protein-synthesis-dependent pathway, and has been used to argue that mitochondrial membrane dysfunction is a primary (rather than secondary) driver of age-associated muscle weakness.

Why Purity Matters

SS-31’s tetrapeptide sequence incorporates the non-natural amino acid Dmt (2′,6′-dimethyltyrosine), which must be correctly incorporated during synthesis to preserve the compound’s aromatic-cationic charge spacing — the structural feature responsible for its preferential inner mitochondrial membrane accumulation. Incorrect Dmt incorporation or substitution with standard tyrosine produces an analogue with substantially reduced membrane affinity and diminished mitochondrial uptake. For researchers using SS-31 as a mechanistic probe for cardiolipin biology or mitochondrial bioenergetics, HPLC purity at ≥99% combined with MS confirmation of the correct molecular weight (including verification of Dmt vs. standard Tyr) is essential for reproducible results. Batch COA documentation should include both HPLC chromatogram and MS spectrum to enable verification of sequence identity.

References:
[1] Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029–50. PMID: 24117398
[2] Siegel MP, et al. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell. 2013;12(5):763–71. PMID: 23692661

Quality & Documentation

Each batch of SS-31 lyophilized powder is individually tested before shipment. Included with every order:

• HPLC purity verification (≥99%)
• Mass spectrometry (MS) identity confirmation
• Batch number for full traceability

COA available upon request before order commitment.

Ordering Information

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FAQ

Q: What is the difference between SS-31 and other Szeto-Schiller peptides (SS-02, SS-20)?
The Szeto-Schiller peptide family shares an alternating aromatic-cationic structural motif designed for inner mitochondrial membrane accumulation, but the specific sequences differ. SS-31 (D-Arg-Dmt-Lys-Phe-NH₂) is the most extensively published member of the family and has been developed furthest in clinical research. SS-02 (D-Arg-Dmt-Lys-Phe-NH₂ with different N-terminus) and SS-20 (Phe-D-Arg-Phe-Lys-NH₂) represent structural variants studied in parallel. SS-31 is the reference compound for cardiolipin-binding studies and is available from Vitaconin with individual batch COA.

Q: What documentation is provided with each order?
Each order of SS-31 lyophilized powder includes a COA with HPLC purity data, MS identity confirmation, and batch number. COA is available before order commitment upon request.

Q: Is there a minimum order quantity?
No minimum order is required. We supply any quantity — contact us for pricing and lead time on your specific order size.

Q: Is SS-31 available in liquid formulation?
Yes, liquid formulation is available on request. Please specify your preferred concentration, solvent, and vial size.

Q: How should SS-31 be stored?
Store unreconstituted lyophilized SS-31 at −20°C, sealed, away from light and moisture. Shelf life is 24 months under proper conditions. Once reconstituted, store at 2–8°C and use within the timeframe specified in the COA.

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