1. Identity and structure
| Property | Detail |
|---|---|
| Common names | SS-31, elamipretide, MTP-131, Bendavia |
| Sequence | D-Arg-Dmt-Lys-Phe-NH2 |
| Dmt | 2′,6′-dimethyltyrosine |
| Length | 4 residues, C-terminal amide |
| Approximate molecular weight | ≈640 Da (free base) |
| Net charge at neutral pH | +3 |
The sequence alternates aromatic and basic residues. The D-arginine at the N-terminus and the C-terminal amide make the molecule resistant to common aminopeptidases, while the dimethyltyrosine residue increases lipophilicity compared with native tyrosine.
2. Origin of the Szeto-Schiller series
The “SS” prefix refers to Hazel Szeto and Peter Schiller, who designed a series of small aromatic-cationic sequences in the early 2000s. The series grew out of work on opioid-receptor ligands; SS-31 is the member without an opioid-binding motif, which made it the subject of later membrane-binding work. Elamipretide is its international nonproprietary name.
3. Membrane phospholipid binding
SS-31 concentrates at the inner membrane of the organelle where it was originally studied. Biophysical work attributes this to electrostatic and hydrophobic interactions with diphosphatidylglycerol, an anionic, four-chain phospholipid that is characteristic of that membrane. The alternating cationic and aromatic side chains are thought to allow the molecule to sit at the membrane interface rather than cross it.
4. Target identification by CRISPR screen
In 2024, Silvaroli and colleagues reported a genome-wide CRISPR knockout screen designed to find the cellular protein that SS-31 depends on. The screen identified phospholipid scramblase 3 (PLSCR3), an enzyme that moves phospholipids between membrane leaflets, as its biological target. This finding added a defined protein partner to the earlier lipid-binding model.
5. Analytical characterization
Identity and purity are confirmed analytically for every lot. Reversed-phase HPLC with UV detection quantifies chromatographic purity, and electrospray mass spectrometry (ESI-MS) confirms that the observed molecular mass matches the theoretical value for SS-31.
Results are reported on a lot-specific certificate of analysis together with appearance, net content and the lot number, which allows any vial to be traced back to its analytical record.
6. Storage and handling
Material is supplied as a lyophilized solid in a sealed vial. Unopened vials are best kept at −20 °C, protected from light and moisture. Allow a vial to equilibrate to room temperature before opening to limit condensation, and record the lot number so the vial can be matched to its certificate of analysis.
A lot-specific certificate of analysis is available for each batch.
Sources
- Silvaroli JA, Bisunke B, Kim JY, et al. Genome-Wide CRISPR Screen Identifies Phospholipid Scramblase 3 as the Biological Target of Mitoprotective Drug SS-31. J Am Soc Nephrol. 2024. doi:10.1681/ASN.0000000000000338. PMID: 38530359. PubMed.
Research Use Only. All products sold by ShortChain Aminos are intended strictly for laboratory research purposes. They are not for human or veterinary use, and nothing in this article constitutes medical advice, usage instructions, or a recommendation of any kind. This content summarizes published third-party research for informational purposes only.