SS-31

Product Details

SS-31 (Elamipretide, MTP-131) — Research Grade Peptide, ≥98% Purity (HPLC)

Cardiolipin-targeting tetrapeptide. Mitochondrial bioenergetics research tool. Lyophilized powder. Lot-specific COA included.

SS-31 (elamipretide) is a synthetic aromatic-cationic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH₂, developed in the Szeto–Schiller laboratories at Weill Cornell and later carried into clinical development as elamipretide (also known as MTP-131 and Bendavia). It is a cell-permeable, mitochondria-targeting peptide designed to protect mitochondrial structure and function.

The peptide’s defining property is its cardiolipin binding in the inner mitochondrial membrane (IMM). Cardiolipin is a dimeric phospholipid found almost exclusively in the IMM, where it constitutes roughly 15–20% of phospholipid content and serves as a scaffold for the protein complexes of the electron transport chain (Complexes I, III, and IV). When cardiolipin is damaged by reactive oxygen species, these complexes dissociate and electron transfer becomes inefficient, generating more ROS in a destructive feedback loop. SS-31 binds cardiolipin through electrostatic attraction (its cationic charge is drawn to cardiolipin’s anionic head groups) and hydrophobic insertion (its aromatic residues embed in the lipid bilayer), preventing cardiolipin peroxidation and maintaining the structural integrity of the electron transport chain.

Unlike conventional mitochondria-targeted molecules such as triphenylphosphonium conjugates, which accumulate in the matrix driven by inner-membrane potential, SS-31 concentrates in the inner membrane itself — and it does so in de-energised mitochondria as well as polarised ones, which means uptake cannot be explained by potential-driven partitioning. The consequence is practical rather than merely mechanistic: a compound whose accumulation is potential-independent still reaches the ischaemic, depolarised mitochondria that are the whole point of studying it.

In oxidatively stressed PC12 cells, SS-31 preserved mitochondrial membrane potential, reduced ROS accumulation, and supported oxidative phosphorylation-related protein integrity. In a mouse thoracic contusion model, SS-31 treatment significantly enhanced locomotor recovery and gait performance, with reduced lesion pathology and increased neuronal preservation at 28 days post-injury.

Supplied as a sterile-filtered, lyophilized powder for in vitro and preclinical research applications. Each lot is independently verified for purity and identity and ships with a Certificate of Analysis.

Specifications

Note: SS-31 is supplied in multiple salt forms with different CAS numbers and molecular weights. The free base (736992-21-5) has a molecular weight of ~639.8 g/mol; the TFA salt (1606994-55-1) is 753.81 g/mol; and the triacetate (1849610-71-4) is 819.94 g/mol. The FDA-approved product Forzinity uses the hydrochloride salt. Verify the exact form, molecular weight, and purity against the Certificate of Analysis supplied with your lot. A COA that lists only “SS-31” without specifying the salt form and molecular weight is not adequate documentation for this product.

Research applications

SS-31 is used in laboratory settings to investigate:

• Cardiolipin stabilization and mitochondrial membrane integrity — binding to cardiolipin in the inner mitochondrial membrane, preventing peroxidation, stabilizing cristae architecture, and maintaining supramolecular organization of electron transport chain complexes I, III, and IV

• Mitochondrial bioenergetics and ATP production — optimization of electron flow through Complexes I, III, and IV, with increased ATP production and reduced superoxide radical generation

• Ischemia-reperfusion injury — reduced infarct size in cardiac ischemia-reperfusion models, with SS-31 reaching ischaemic, depolarised mitochondria due to its potential-independent uptake mechanism

• Heart failure and cardiac function — normalized mitochondrial dynamics in canine heart failure models, with chronic therapy improving left ventricular and mitochondrial function

• Neuroprotection and spinal cord injury — enhanced locomotor recovery, reduced lesion pathology, and increased neuronal preservation at 28 days post-injury in mouse thoracic contusion models, with attenuated apoptosis signaling (reduced cleaved caspase-3 and Bax, increased Bcl-2)

• Age-related mitochondrial decline — improved ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT), with direct binding to the mitochondrial ADP transporter

• Pulmonary arterial hypertension and acute lung injury — attenuated pulmonary arterial hypertension and acute lung injury in rodent models

• Skeletal muscle performance in HFpEF — improved mitochondrial function and contractile function in a heart failure with preserved ejection fraction (HFpEF) rat model, highlighting cardiolipin stabilization as a key modulator of skeletal muscle dysfunction

• Barth syndrome models — restoration of mitochondrial morphology in tafazzin-deficient heart by affecting proteins involved in dynamic processes and mitophagy in TazKD mice

• Analytical method development — LC-MS/MS quantification and reference standard preparation for tetrapeptide analysis in biological matrices

Handling and storage

Reconstitute under aseptic conditions using sterile water or an appropriate aqueous buffer. SS-31 is soluble in water. Aliquot immediately after reconstitution to avoid repeated freeze-thaw cycles. Lyophilized powder is stable for up to 2 years at −80 °C or 1 year at −20 °C under sealed, desiccated, light-protected conditions. Reconstituted solutions should be stored at −80 °C for 6 months or −20 °C for 1 month. Do not freeze reconstituted solution repeatedly.