GMP PCL SS-31 12mg

SS-31 (also known as elamipretide) is a synthetic, mitochondria-targeted tetrapeptide (D-Arg-Dmt-Lys-Phe-NH₂) that exhibits high affinity for the anionic phospholipid cardiolipin, which is located almost exclusively in the inner mitochondrial membrane (IMM). This peptide is characterized by an alternating aromatic–cationic motif that enables dual hydrophobic and electrostatic interactions with cardiolipin, facilitating its selective localization to mitochondria (Chavez et al. 2020). Structural analyses using cross-linking mass spectrometry have revealed that SS-31 interacts directly not only with cardiolipin but also with several cardiolipin-associated proteins integral to oxidative phosphorylation and mitochondrial metabolism, including components of complexes III, IV, and V of the electron transport system, ADP/ATP translocase, and creatine kinase (Chavez et al. 2020). These interactions are positioned near known cardiolipin-binding regions, suggesting a stabilizing influence on mitochondrial inner membrane architecture and respiratory supercomplex organization.

In aged tissues, SS-31 has been shown to preserve mitochondrial structure and improve cellular integrity. Transmission electron microscopy of renal glomeruli demonstrated that aged mice treated with SS-31 exhibited restored mitochondrial cristae and reduced structural damage compared to age-matched controls, along with lower expression of reactive oxygen species–generating enzymes such as Nox4 (Sweetwyne et al. 2017). Additionally, mitochondrial gene expression associated with the electron transport chain (e.g., Ndufa9 and Cox IV) was enhanced following short-term SS-31 administration (Sweetwyne et al. 2017). At the cellular level, SS-31 treatment was associated with reduced markers of senescence (p16, SA-β-Gal), decreased extracellular matrix accumulation (collagen IV), and improved structural integrity of podocytes and endothelial cells in aged kidneys (Sweetwyne et al. 2017).

Comprehensive proteomic and structural analyses have demonstrated that SS-31 interacts with mitochondrial proteins involved in both ATP production and 2-oxoglutarate metabolism, including components of the electron transport chain and the tricarboxylic acid cycle (Chavez et al. 2020). This mechanistic evidence supports its role in stabilizing mitochondrial bioenergetics through modulation of cardiolipin–protein interactions and preservation of mitochondrial ultrastructure (Zhu et al. 2022; Chavez et al. 2020). Collectively, these studies describe SS-31 as a unique mitochondrial-targeted peptide that binds cardiolipin, interacts with critical respiratory and metabolic proteins, and helps maintain mitochondrial structure and function in cellular and tissue models of aging and stress.