PROMO!
First order? Get 10% OFF with this code: 1storder
SS-31 (Elamipretide) is a synthetic mitochondria-targeted tetrapeptide that selectively binds cardiolipin within the inner mitochondrial membrane and is studied for its effects on mitochondrial membrane and bioenergetic processes.
SS-31, which is also called elamipretide and MTP-131, is a synthetic tetrapeptide directed at the mitochondria and is a member of the Szeto–Schiller (SS) peptide family. Its sequence is H-D-Arg-Dmt-Lys-Phe-NH₂, in this sequence Dmt stands for 2′,6′-dimethyltyrosine. The peptide has residues that alternate between cationic and aromatic ones, which confers on it particular physicochemical properties relevant to its interaction with mitochondrial membranes.
A great deal of research in the laboratory has concentrated on the way in which SS-31 interacts with cardiolipin, an anionic phospholipid which is concentrated in the inner mitochondrial membrane. Experiments based on biophysical methods and computational approaches show that SS-31 enters the interfacial areas of the membrane in a way that is affected by the surface charge of the membrane. Further investigations into the electrostatic interactions between the basic amino acid residues of the peptide and the phosphate groups of cardiolipin, as well as those involving the aromatic residues of the peptide in the lipid environment, have been carried out using NMR and model lipid systems.
SS-31 therefore provides a defined molecular probe for studying peptide–lipid interactions, mitochondrial membrane biophysics, cardiolipin-associated processes, and membrane surface electrostatics. Mass-spectrometry-based research has additionally examined SS-31 interactions with mitochondrial proteins associated with cardiolipin-containing environments and oxidative phosphorylation.
In any research context, SS-31 should be specified by its particular tetrapeptide sequence and its modified amino acids, together with its C-terminal amidation, molecular identity, purity, and the analytical data associated with the specific batch. Any talk about its mitochondrial or cardiolipin-related activity must be based on results from controlled experiments and should not be taken as indicating any therapeutic benefit or as suggesting that it is suitable for use in humans.
SS-31, also known as elamipretide or MTP-131, is a synthetic tetrapeptide composed of four residues: D-Arg-Dmt-Lys-Phe-NH₂, where Dmt represents the non-standard aromatic amino acid 2′,6′-dimethyltyrosine. The molecule also contains a D-arginine residue at its N-terminus and an amidated phenylalanine at the C-terminus.
The peptide has an alternating sequence of cationic and aromatic residues, arginine and lysine having side chains that carry a positive charge while dimethyltyrosine and phenylalanine supply the aromatic properties. This compact structure, consisting of aromatic and cationic residues, is a characteristic structural feature of the Szeto–Schiller peptide family.
Authoritative chemical databases list the molecular formula of the free peptide as C₃₂H₄₉N₉O₅, the average molecular weight as approximately 639.8 g/mol, and the CAS number as 736992-21-5.
Since SS-31 has no cysteine residues, its structure does not include disulfide bonds derived from cysteine; rather, its molecular identity is due to the defined stereochemistry of the peptide, the inclusion of the modified Dmt residue, and C-terminal amidation.
Different counterion or salt forms can have molecular compositions that differ from the free peptide; for example, a distinct trifluoroacetate (TFA) form is cataloged separately. For research material, the precise chemical form, sequence, molecular identity and purity should therefore be assessed against the batch-specific Certificate of Analysis rather than assumed from the SS-31 name alone.
SS-31, also known as elamipretide, is investigated primarily through its interactions with the inner mitochondrial membrane. Unlike peptides whose activity is centered on a conventional cell-surface receptor, SS-31 appears to interact directly with lipid membranes, with particular research attention given to cardiolipin-rich membrane environments. Its precise molecular mechanism continues to be refined through biochemical, biophysical and computational studies.
Cardiolipin and Membrane Interactions
Cardiolipin is an anionic phospholipid enriched within the inner mitochondrial membrane. Experimental and molecular-dynamics studies indicate that the positively charged groups of SS-31 interact with negatively charged lipid phosphates, while its aromatic residues can partition further into the membrane interface. The strength of this interaction has been shown to depend substantially on membrane surface charge.
Membrane Electrostatics
Biophysical research suggests that SS-31 can alter the electrostatic properties of lipid bilayers without disrupting the lamellar membrane structure. These changes may influence the distribution of ions and proteins at the membrane interface. Experiments have, for example, demonstrated changes in interfacial calcium distribution following SS-31 binding.
Cardiolipin-Associated Protein Interactions
SS-31 has also been studied in connection with proteins associated with cardiolipin-rich mitochondrial membranes. Experiments using cross-linking mass spectrometry found that the proteins associated with SS-31 were involved in oxidative phosphorylation and mitochondrial metabolic processes, and several of the interaction areas were located near known cardiolipin-binding sites.
Cytochrome c Research
Another experimental area concerns the cardiolipin–cytochrome c interaction. Laboratory studies have investigated whether SS-31 modifies the molecular environment of this complex and influences the balance between the electron-transfer and peroxidase-associated states of cytochrome c.
SS-31 serves as a well-defined research peptide for the study of peptide–lipid interactions, membrane electrostatics, the organization of proteins associated with cardiolipin, and the biophysics of mitochondrial membranes. However, these mechanisms are still subjects of molecular investigation and must not be extended to any claims regarding therapeutic effectiveness or appropriateness for use in humans.
This summary reflects findings reported in published preclinical and in vitro research. The original studies supporting this information are listed in the references.
SS-31 has been studied in great detail with regard to cardiolipin, an anionic phospholipid which is concentrated in the inner mitochondrial membrane. Experiments carried out using liposomes and bicelles containing cardiolipin have investigated peptide–lipid interactions by means of techniques such as NMR and fluorescence spectroscopy, thus yielding molecular information on how SS-31 associates with membrane environments.
Biophysical and computational models have been used to investigate how SS-31 influences lipid packing and membrane-surface electrostatics. Research indicates that the peptide partitions into membrane interfacial regions in a manner strongly influenced by surface charge, providing a model for studying aromatic-cationic peptide interactions with lipid bilayers.
Laboratory research has looked at SS-31 in experimental systems that include cardiolipin and cytochrome c. Such systems enable the researchers to study the effect of peptide binding on the molecular arrangement and functional properties of cardiolipin–protein interactions under controlled conditions.
Chemical cross-linking together with mass spectrometry was employed in order to identify the proteins associated with SS-31 in isolated mitochondria; the interactors identified were cardiolipin-binding proteins that take part in oxidative phosphorylation and in metabolic processes associated with 2-oxoglutarate, and in several cases the peptide interaction domains were found near the known cardiolipin-binding domains.
SS-31 has likewise been studied in experimental models that look at ion distribution at membrane interfaces. Studies in the field have shown that peptide association can alter the distribution of calcium at the interface, thus providing a laboratory system for investigating the relationships between membrane electrostatics, lipid composition and divalent cations.
Experimental models have applied electron microscopy, measurements of mitochondrial respiration, and analysis of the membranes in order to study SS-31 in relation to mitochondrial membrane structure. The methods available allow for an examination of the connections between interactions between cardiolipin-associated peptides and the structural arrangement of mitochondrial membranes and cristae.
Overall, these research areas are best presented as molecular, biochemical and biophysical investigations rather than as evidence of therapeutic efficacy or suitability for human use.
The analytical verification of the SS-31 Peptide should aim at verifying its molecular identity, ensuring structural consistency, and checking its chromatographic purity. Reverse-phase high-performance liquid chromatography (RP-HPLC) may be employed to separate the main SS-31 component from detectable peptide-related impurities and to give a quantitative evaluation of the chromatographic purity. Certificates that have been published for the characterized elamipretide reference material include both HPLC analysis and testing for structural identity.
By using mass spectrometry, for example ESI-MS or LC-MS, complementary information regarding identity can be obtained by comparing the molecular mass that is observed in the experiment with the molecular mass that is expected for SS-31. This is especially important since SS-31 contains the non-standard 2′,6′-dimethyltyrosine (Dmt) residue, D-arginine and has a amidation at the C-terminus. The present analytical testing methods involve combining chromatographic separation with confirmation of identity on the basis of mass.
For research material, results should be assessed against the batch-specific Certificate of Analysis, with attention to peptide identity, purity, chemical form and the analytical methods used.
Store SS-31 research material at 2–8°C. Keep the material in its original container and keep the container closed during storage. Protect it from moisture and direct light.
For laboratory handling, open the container only when needed and limit the time the material remains outside refrigerated storage. Use clean laboratory equipment and standard procedures to prevent contamination.
Follow the laboratory SOP established for the specific research application when handling SS-31.
SS-31 is a synthetic tetrapeptide from the Szeto–Schiller peptide family and its specific sequence includes both standard and modified amino acid residues; it is not a naturally occurring mitochondrial peptide.
Dmt is short for 2′,6′-dimethyltyrosine, an altered aromatic amino acid residue located at the second position in SS-31. The aromatic property of Dmt is what gives the peptide its characteristic alternating arrangement of aromatic and cationic groups.
SS-31 is a compact peptide consisting of four amino acid residues and having the sequence D-Arg-Dmt-Lys-Phe-NH₂; it includes the cationic amino acids arginine and lysine together with the aromatic ones Dmt and phenylalanine and has a C-terminal amidation.
Cardiolipin is a particular anionic phospholipid which has two phosphate groups at its head end and four acyl chains; it is concentrated in the inner mitochondrial membrane and is often included in model membranes that are used for studying interactions between SS-31 and this lipid.
Research has examined both electrostatic and hydrophobic interactions between SS-31 and lipid membranes. Experimental evidence indicates that its membrane association is strongly influenced by negative surface charge, while its aromatic residues can interact with the membrane interfacial environment.
Techniques such as RP-HPLC and mass spectrometry can provide complementary information about SS-31 purity and molecular identity. More specialized research methods, including NMR and mass-spectrometry-based approaches, can also be used when investigating its structure and molecular interactions.
Mass spectrometry provides molecular-mass information that can be compared with the expected molecular characteristics of SS-31. LC-MS or tandem MS approaches can provide additional structural information and can also be used when investigating SS-31-associated molecular interactions; cross-linking mass spectrometry, for example, has been used to identify mitochondrial proteins associated with SS-31.
Batch-specific verification provides analytical information about the particular research material supplied, rather than relying only on the general SS-31 name. The relevant Certificate of Analysis and supporting analytical data should therefore be reviewed when assessing the stated identity, purity, and chemical form of an individual batch.
SS-31 is offered exclusively for laboratory research and scientific or analytical purposes. It is not intended for human or animal consumption or administration, or for use in diagnosis, treatment, prevention, or management of any disease or condition.
All information on this page is provided for scientific and technical research purposes only. SS-31 is not intended for clinical practice or veterinary use.
