Description

SS-31 (Elamipretide) is a synthetic, cell-permeable tetrapeptide belonging to the Szeto-Schiller (SS) family of aromatic-cationic peptides. Unlike conventional antioxidants that indiscriminately scavenge reactive oxygen species (ROS) throughout the cell, SS-31 selectively concentrates within the inner mitochondrial membrane (IMM).

Due to its alternating aromatic and cationic amino acid motif, it crosses the plasma and outer mitochondrial membranes in an energy-independent manner, independent of the mitochondrial membrane potential.

In experimental pharmacology and bioenergetic research, SS-31 serves as a highly targeted chemical probe. It binds specifically to cardiolipin, a unique and critical phospholipid exclusively expressed on the inner mitochondrial membrane. By anchoring to cardiolipin, SS-31 stabilizes cristae architecture, promotes the efficient assembly of respiratory supercomplexes, and prevents the pathological opening of the mitochondrial permeability transition pore (mPTP) during severe cellular stress events, such as ischemia-reperfusion (I/R) injury and neurodegeneration.

Biochemical Characteristics

Chemically, SS-31 is engineered with modified, non-naturally occurring amino acids to ensure absolute resistance to rapid proteolytic degradation while maintaining a highly specific binding affinity for anionic lipid bilayers.

• Sequence/Structure: Tetrapeptide; D-Arg-Dmt-Lys-Phe-NH2 (where Dmt represents 2,6-dimethyltyrosine).
• Permeability: Possesses a net charge of +3 at physiological pH, allowing it to efficiently penetrate cell membranes while selectively accumulating (1000- to 5000-fold) at the cardiolipin-rich inner mitochondrial membrane.
• Stability: Supplied as a lyophilized salt to ensure structural integrity. The inclusion of D-arginine protects the peptide from aminopeptidase cleavage, radically extending its experimental half-life in physiological assays.
• Specificity: Selectively prevents pathological ROS generation directly at the source (Complex I and III of the ETC) without disrupting the necessary physiological redox signaling required for healthy cellular homeostasis.

Chemical Properties