SS-31

SS-31 is a synthetic tetrapeptide — D-Arg-Dmt-Lys-Phe-NH2, in which Dmt is 2,6-dimethyltyrosine — supplied as a lyophilized powder for laboratory research use only. It appears in the literature under the name elamipretide and under the development codes MTP-131 and Bendavia.

Its alternating aromatic and cationic residues give it a charge-and-hydrophobicity profile that the mechanistic literature describes as concentrating the peptide at the inner mitochondrial membrane without depending on membrane potential, which is the structural feature most of that work is concerned with.

The reported interactions center on cardiolipin, a phospholipid largely confined to the inner mitochondrial membrane. Biophysical work characterizes binding to lipid bilayers and modulation of membrane surface electrostatics; chemical-crosslinking mass spectrometry has been used to map which mitochondrial proteins sit within range of the bound peptide.

Structure-activity work across related tetrapeptide analogues examines which residues account for the observed membrane association. The literature listed below is in-vitro, cell-free, and preclinical: it reports binding measurements and bioenergetic readouts in isolated systems.

Reported mechanism · literatureIn the mechanistic literature SS-31 is characterized as a mitochondria-targeting tetrapeptide that associates with cardiolipin in the inner mitochondrial membrane and alters the local lipid environment and surface charge, with reported consequences for the organization of electron-transport components as measured in isolated mitochondria and in cell-free bilayer systems.