Elamipretide structure explained: the D-Arg-Dmt-Lys-Phe-NH2 tetrapeptide sequence, its molecular formula, net charge, and how it targets mitochondria.
Elamipretide is a synthetic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, where Dmt stands for 2',6'-dimethyltyrosine. Its molecular formula is C32H49N9O5, and its molecular weight is about 639.8 g/mol. The molecule is a short, linear, positively charged peptide designed to concentrate in mitochondria rather than a folded protein with a fixed three-dimensional shape.
That sequence explains nearly everything about how elamipretide behaves. Two residues carry positive charges, one is a modified aromatic amino acid, and the C-terminus is capped as an amide. Together those features control membrane binding, enzyme resistance, and antioxidant activity.
The Elamipretide Sequence, Residue by Residue
Elamipretide contains exactly four amino acids, which makes it a tetrapeptide. Its sequence is written as D-Arg-Dmt-Lys-Phe-NH2, and the "NH2" shows that the C-terminus is an amide instead of a free carboxylic acid.
| Position | Residue | Structural role |
|---|---|---|
| 1 (N-terminus) | D-Arg | Carries a positive charge and blocks aminopeptidase attack |
| 2 | Dmt (2',6'-dimethyltyrosine) | Aromatic antioxidant residue that scavenges free radicals |
| 3 | Lys | Second positive charge that supports cardiolipin binding |
| 4 (C-terminus) | Phe-NH2 | Aromatic residue; the amide cap removes the free carboxylate |
The D-arginine at position 1 is a key structural detail. Natural peptides almost always begin with L-amino acids, and proteases recognize that stereochemistry. Using the D-form makes elamipretide far more stable in blood and tissue.
Dmt at position 2 is the other signature residue. It is a tyrosine analog with two extra methyl groups on the aromatic ring, and those groups make it a more effective electron donor and radical quencher.
Molecular Formula and Physical Properties
The full molecular formula is C32H49N9O5. Three ionizable groups are positively charged at physiological pH: the D-arginine side chain, the lysine side chain, and the N-terminal amine. That produces a net charge of roughly +3.
| Property | Value |
|---|---|
| Molecular formula | C32H49N9O5 |
| Molecular weight | Approximately 639.8 g/mol |
| Peptide length | 4 residues (tetrapeptide) |
| Net charge at pH 7.4 | Approximately +3 |
| N-terminus | Free D-arginine amine |
| C-terminus | Amide (Phe-NH2) |
| Appearance | White to off-white lyophilized powder |
| Solubility | Water-soluble, typical of cationic peptides |
Because the chain is so short, elamipretide does not fold into a stable helix or beta sheet. It behaves more like a flexible, extended cation in solution than like the compact globular proteins most people picture when they think about peptide drugs.
Why the Structure Drives Mitochondrial Targeting
The positive charges are not decorative. The inner mitochondrial membrane is rich in cardiolipin, a negatively charged phospholipid, and elamipretide's arginine and lysine residues bind it through electrostatic attraction. The mitochondrial membrane potential then pulls the peptide inward.
Once bound, elamipretide helps stabilize cardiolipin clusters and supports the curved cristae architecture where the electron transport chain operates. The Dmt residue adds a second job by acting as a radical scavenger near the membrane.
Elamipretide's net positive charge is what drives its accumulation inside mitochondria.
The D-arginine residue makes elamipretide resistant to aminopeptidase degradation.
How Elamipretide Compares with Other Peptides
Size and charge separate elamipretide from larger research peptides. The table below compares three peptides that are often discussed together.
| Peptide | Class | Length | Key structural features |
|---|---|---|---|
| Elamipretide | Mitochondria-targeted synthetic peptide | 4 residues | Cationic D-Arg-Dmt-Lys-Phe-NH2; no stable secondary structure |
| Retatrutide | Triple GLP-1, GIP, and glucagon receptor agonist | About 39 residues | Long modified backbone that folds into helical regions |
| BPC-157 | Synthetic pentadecapeptide | 15 residues | Fragment of a gastric protein with a partial helical tendency |
Elamipretide is too short to form a meaningful secondary structure of polypeptide chains such as alpha helices or beta sheets. Retatrutide chemical structure, by contrast, is long enough to fold into helices that shape receptor binding and protect the peptide from breakdown.
BPC-157 sits between the two. It is longer than elamipretide but much shorter than retatrutide, and its partial helix contributes to its resistance to acid and enzymes.
Elamipretide Uses and Clinical Trial Status
Research has focused on conditions tied to mitochondrial dysfunction. Reported elamipretide uses in clinical programs include Barth syndrome, primary mitochondrial myopathy, heart failure with reduced ejection fraction, and Leber hereditary optic neuropathy.
Results have been mixed. Some early studies showed improvements in exercise capacity or cardiac measurements, while larger elamipretide clinical trial programs in heart failure and mitochondrial myopathy did not consistently hit their primary endpoints.
Elamipretide is not FDA-approved for general human use in the United States as of 2025. It has received orphan drug designation for Barth syndrome, and the manufacturer has continued to pursue regulatory review.
Anyone considering elamipretide should talk with a healthcare professional first. It remains an investigational product, and long-term safety data are still limited.
Pronunciation, Naming, and Storage
The common elamipretide pronunciation is "el-uh-MIP-reh-tide," with the stress on the third syllable. The compound also appears in the literature as SS-31 and MTP-131, and Forzinity is the proposed brand name.
Suppliers ship elamipretide as a lyophilized powder that should be stored frozen, typically at -20 °C or colder, and protected from light. Reconstituted solutions should stay cold and be used within the window stated on the certificate of analysis.
Handling matters because poor storage can cause aggregation or degradation even when the primary structure stays intact. Researchers working with related compounds often apply the same cold-chain habits they use for other short peptides.
Frequently Asked Questions
What is the amino acid sequence of elamipretide?
Elamipretide's sequence is D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine. It is a four-residue peptide with a C-terminal amide instead of a free acid. The N-terminal arginine is in the D-configuration, which is unusual for natural peptides and helps the molecule resist enzyme breakdown.
Is elamipretide approved by the FDA?
No. As of 2025, elamipretide remains an investigational drug in the United States. It holds orphan drug designation for Barth syndrome, and regulatory review has been ongoing. It should not be used outside of a clinical trial or without supervision from a healthcare professional.
How is elamipretide different from BPC-157?
Elamipretide is a synthetic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, while BPC-157 is a 15-amino-acid peptide derived from a gastric protein. Elamipretide carries a net positive charge of about +3 and is designed to bind cardiolipin in mitochondria. BPC-157 has different structural features and proposed mechanisms, so the two are not interchangeable.
This page provides educational research information and does not replace medical advice, diagnosis, or treatment.