SS-31

SS-31 is a four-residue peptide, and almost everything interesting about it is packed into how unusual those four residues are. Three of the four positions carry something non-standard, which is a remarkable density of modification for a tetrapeptide.

Identity and classification

SS-31 is catalogued as a mitochondria-targeted peptide. That is a description of the compound class as reference suppliers file it, and no receptor target is assigned to it.

One point of accuracy worth making explicitly: the statement that SS-31 binds cardiolipin in the inner mitochondrial membrane is repeated very widely. We could not source it from any reference-supplier catalogue entry — it appears in reseller and secondary material only. It is therefore not stated here as fact. If the mechanism matters to your work, source it from the primary literature rather than from a supplier page, including this one.

The compound carries several names. Elamipretide is the International Nonproprietary Name; SS-31 is the original laboratory designation, where SS denotes the Szeto–Schiller peptide series; MTP-131 and Bendavia are development and trade designations. All four refer to the same molecule.

Structure

D-Arg-Dmt-Lys-Phe-NH₂, reading from the N-terminus:

• D-arginine at position 1. A D-amino acid, inverting the stereocentre and conferring protease resistance at the N-terminus.
• Dmt at position 2. 2,6-dimethyl-L-tyrosine — a tyrosine bearing methyl groups on both positions flanking the phenolic hydroxyl. This is a specialist residue, not commercially trivial, and its presence is the main reason this tetrapeptide is more expensive to make than its length suggests.
• Lysine at position 3 — standard.
• Phenylalanine at position 4, as a C-terminal primary carboxamide.

The defining motif is the alternating aromatic–cationic pattern: cationic D-Arg, aromatic Dmt, cationic Lys, aromatic Phe. That alternation is the structural feature the compound class is named for.

Specification and characterisation

• RP-HPLC purity at 214 nm. Both Dmt and Phe absorb around 280 nm, and the phenol of Dmt gives the stronger signal.
• Mass confirmation against 639.80. At this size a singly-charged ion is straightforward.
• Stereochemical purity. As with ipamorelin, the D-residue at position 1 means epimerisation produces a diastereomer of identical mass, invisible to mass spectrometry. Chiral analysis or diastereomer-resolving chromatography is required. This is the specification point most often absent from certificates for D-amino-acid peptides.
• Dmt identity. The substitution of ordinary tyrosine for 2,6-dimethyltyrosine is a −28 Da change and would be caught by mass. Given that Dmt is the expensive residue, this is a substitution worth confirming rather than assuming.
• Amidation completeness. The free acid differs by +1 Da.
• Counter-ion and net peptide content. Two cationic residues on a four-residue peptide means a proportionally heavy counter-ion burden. Note the separate acetate registry number in the table.

Handling and stability

Store sealed at 2–8 °C, dry, protected from light. Equilibrate in a desiccator before opening.

There is no cysteine and no methionine, so neither disulfide chemistry nor sulfoxide formation applies. The phenolic hydroxyl of Dmt is oxidisable in principle, though the two flanking methyl groups sterically hinder it — one of the incidental consequences of that substitution.

The peptide is highly water-soluble; reference catalogues report solubility in PBS at pH 7.2 at 10 mg/mL.

Related compounds in this library

Ipamorelin is the closest analogue in construction — another short peptide built largely from non-standard residues, with the same stereochemical characterisation requirement. MOTS-c and NAD⁺ share the mitochondrial research grouping but no chemistry.

References

Chemical, specification and analytical sources. This list is deliberately limited to chemistry and analytical references.

• Cayman Chemical 33302, MTP-131 acetate — formula, molecular weight, sequence, salt form, solubility
• MedChemExpress, elamipretide — registry and specification data
• ChemicalBook, CAS 736992-21-5 — registry confirmation
• Bachem, Handling and Storage Guidelines for Peptides — lyophilised solid handling

Cosmic Aminos supplies this material as a laboratory reagent for in-vitro research use only. It is not a drug, food, cosmetic or dietary supplement, is not approved by the Food and Drug Administration for any use, and is not for human or veterinary consumption. No dosing, administration or preparation guidance is provided.