SS-31 (Elamipretide)

Design of the molecule

The Szeto–Schiller series was developed around an alternating aromatic–cationic motif that carries a net positive charge at physiological pH. Substituting D-arginine at position one and dimethyltyrosine at position two produces a peptide that resists aminopeptidase degradation while retaining the charge distribution thought to drive membrane association. At 639.80 g/mol it is one of the smallest peptides in routine mitochondrial research use.

Cardiolipin and membrane studies

Reported mechanisms in the peer-reviewed literature include:

• Selective association with cardiolipin in the inner mitochondrial membrane, independent of membrane potential
• Effects on cristae curvature and membrane packing observed by electron microscopy in isolated mitochondria
• Modulation of cytochrome c peroxidase activity when cytochrome c is complexed with cardiolipin
• Reduced mitochondrial reactive oxygen species output in stressed preparations

Analytical and stability notes

The peptide is highly water-soluble and stable in solution relative to longer sequences, but the free tyrosine-like Dmt residue is still light-sensitive. Purity is verified by reverse-phase HPLC and identity by ESI-MS against the expected 639.8 Da monoisotopic profile.

Because the tetrapeptide is small and highly soluble, it is often used as a positive control when benchmarking newer mitochondria-targeting chemotypes, and its behaviour in isolated mitochondria is well enough characterised that deviations usually point to a preparation problem rather than to biology. Investigators comparing lots typically confirm retention time and mass before pooling material across experiments.

Bring the vial to room temperature before breaking the seal, then introduce diluent slowly against the glass wall so the lyophilized cake dissolves without foaming. SS-31 goes into aqueous solution readily; swirl rather than shake and inspect for complete clarity before use. Protect solutions from ambient light, keep them at 2–8 °C, and split larger preparations into single-use aliquots to avoid repeated freeze–thaw cycles. Label every aliquot with the lot number and reconstitution date so results can be traced back to the Certificate of Analysis. Store unopened vials at −20 °C.