SHuffle Peptide (Elamipretide Context)
Also known as: SS peptide class, Szeto-Schiller peptides, Mitochondria-targeted peptides
Overview
The Szeto-Schiller (SS) peptide class, developed by Hazel Szeto and Peter Schiller, represents a family of cell-permeable, mitochondria-targeted aromatic-cationic peptides that selectively accumulate 1000-fold in the inner mitochondrial membrane without relying on the transmembrane potential. SS-31 (elamipretide) is the lead compound, but the structural class includes SS-02, SS-19, and SS-20 with varying selectivity for different mitochondrial targets. The SS peptide approach established the principle that cardiolipin-targeting peptides could restore mitochondrial architecture and bioenergetics in aging and disease.
Mechanism of Action
All SS peptides share an alternating aromatic-cationic motif (Phe or Dmt aromatic residues alternating with Arg or Lys cationic residues) that confers mitochondrial membrane affinity via electrostatic and hydrophobic interactions with cardiolipin. Once localized to the inner mitochondrial membrane, SS peptides: (1) protect cardiolipin from oxidation by cytochrome c, restoring electron transfer efficiency; (2) maintain cristae junction structure critical for Complex I/III/IV supercomplex assembly; (3) reduce electron leak and ROS production at Complexes I and III; (4) restore ATP synthase efficiency. The net result is enhanced oxidative phosphorylation, reduced ROS, and improved mitochondrial dynamics.
Potential Benefits
- Structural class validating mitochondria-targeted peptide approach
- Cardiolipin protection restoring electron transport chain efficiency
- Cristae structure preservation essential for supercomplex assembly
- Reduced mitochondrial ROS production
- Multiple members allow selective targeting of different mitochondrial functions
- Inspiration for next-generation mitochondrial therapeutics
Dosage Protocols
The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.
| Beginner | Clinical use / research only |
| Intermediate | N/A |
| Advanced | N/A |
| Cycle Duration | Months to years (chronic mitochondrial disease) |
Same compound as SS-31. 'SHuffle' is a contextual reference in Stealth BioTherapeutics development. Phase III submitted for Barth syndrome.
Use our Reconstitution Calculator to determine exact syringe units for your protocol.
Routes of Administration
Subcutaneous Injection High
Clinical trial route (Stealth BioTherapeutics).
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving SHuffle Peptide (Elamipretide Context):
Mitochondrial Support Stack
Research combination for mitochondrial function — cardiolipin protection, AMPK activation, mitophagy support.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Storage | Refrigerate at 2-8°C after reconstitution. Do not freeze reconstituted solution. |
|---|
Typical vial sizes: 40 mg. Add bac water slowly down the side of the vial, swirl gently — do not shake. Use insulin syringe for precise dosing.
Need exact syringe measurements?
Amino Acid Sequence
SS-31: D-Arg-2',6'-Dmt-Lys-Phe-NH2; SS-02: D-Arg-Dmt-Lys-Phe-NH2 (similar)
Side Effects & Safety
- See SS-31 entry for lead compound data
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
Pregnancy / Lactation
Bleeding Disorders
Active Skin Infection at Injection Site
Pharmacokinetics
| Half-Life | ~2-4 hours plasma; mitochondrial accumulation prolongs action |
|---|---|
| Storage | Store lyophilized peptide at -20°C (long-term) or 2-8°C (short-term, under 30 days). Reconstituted: refrigerate at 2-8°C and use within 28-30 days. Protect from light. Do not freeze reconstituted solution. |
Synergistic Compounds
The following compounds have been studied alongside SHuffle Peptide (Elamipretide Context) for potential complementary or synergistic effects:
Learn More
References & Further Reading
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