SS-31: A Tetrapeptide That Targets the Inner Mitochondrial Membrane

SS-31 is a synthetic tetrapeptide with the sequence D-Arg–2′,6′-dimethyltyrosine–Lys–Phe-NH2. It belongs to the Szeto–Schiller (SS) family of peptides designed to reach mitochondria.

Mechanism under study

In a 2014 review in the British Journal of Pharmacology, First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics, Hazel Szeto describes the evidence that SS-31 selectively interacts with cardiolipin, a phospholipid characteristic of the inner mitochondrial membrane. The review discusses how this interaction is studied in isolated mitochondria, cells and animal models, with a focus on electron transport and mitochondrial bioenergetics.

Notable chemistry

• Unnatural residues. The D-arginine and dimethyltyrosine residues are not found in standard proteins; they are chosen to influence stability and properties.
• Alternating charges. The sequence alternates aromatic and basic residues, giving a molecule with a net positive charge at physiological pH.
• Small size. As a tetrapeptide with an amidated C-terminus, its identity is readily confirmed by mass spectrometry.

Analytical considerations

Because SS-31 includes a D-amino acid, stereochemical purity is a relevant quality attribute; an analytical method should be able to distinguish the intended stereoisomer from diastereomeric impurities.

SS-31 supplied by ICU RESEARCH is for laboratory research use only.