SS-31 and MOTS-C are two structurally different peptides associated with mitochondrial research. Although both appear in scientific literature involving mitochondria, they differ significantly in amino acid sequence, molecular weight, chemical composition, and origin.
SS-31, also known as elamipretide or MTP-131, is a synthetic tetrapeptide containing four amino acid residues. MOTS-C is a 16-amino-acid peptide encoded by a short open reading frame within mitochondrial DNA.
One of the most important distinctions between SS-31 vs. MOTS-C is that SS-31 is synthetically designed, while MOTS-C belongs to the family of mitochondrial-derived peptides encoded by the mitochondrial genome.
Their different molecular structures also create distinct considerations for peptide identification, analytical testing, and laboratory documentation.
This article compares their chemical properties, amino acid sequences, molecular origins, and research classifications to explain how these peptides differ.
What Is SS-31 Peptide?
SS-31 is a synthetic tetrapeptide belonging to the Szeto-Schiller family of peptides.
It is also known by the names elamipretide, MTP-131, and the historical development designation Bendavia.
SS-31 consists of four amino acid residues arranged in a specific sequence:
D-Arg-Dmt-Lys-Phe-NH₂
Here, Dmt represents 2,6-dimethyltyrosine, a chemically modified aromatic amino acid.
The peptide contains a D-amino acid residue, a modified tyrosine residue, and a C-terminal amide.
These structural features distinguish it from peptides made entirely from conventional L-amino acids.
SS-31 has been studied in laboratory research involving cardiolipin-containing mitochondrial membranes, peptide-lipid interactions, and membrane electrostatics.
For additional scientific details, researchers can explore Orion Peptides’ article on SS-31 and mitochondrial cardiolipin research.
Chemical Properties of SS-31
| Property | SS-31 |
|---|---|
| Common name | SS-31 |
| Alternative name | Elamipretide |
| Research designation | MTP-131 |
| Peptide sequence | D-Arg-Dmt-Lys-Phe-NH₂ |
| Amino acid residues | 4 |
| Molecular formula | C₃₂H₄₉N₉O₅ |
| Molecular weight | 639.8 g/mol |
| CAS number | 736992-21-5 |
| PubChem CID | 11764719 |
| Peptide classification | Synthetic tetrapeptide |
| C-terminal modification | Amidation |
These specifications describe the parent elamipretide structure. A supplied salt preparation may have additional counterions that are not represented by the parent molecular formula.
The chemical identifiers can be verified using the PubChem Elamipretide compound record.
What Is MOTS-C Peptide?
MOTS-C stands for Mitochondrial Open Reading Frame of the 12S rRNA-c.
Unlike SS-31, which was developed as a synthetic peptide, MOTS-C is encoded by a short open reading frame within the human mitochondrial genome.
It was described in a 2015 research paper published in Cell Metabolism.
MOTS-C belongs to a group of molecules known as mitochondrial-derived peptides (MDPs).
These peptides are associated with short open reading frames within mitochondrial DNA.
The standard MOTS-C sequence contains 16 amino acid residues:
MRWQEMGYIFYPRKLR
This sequence is substantially longer than that of SS-31.
MOTS-C also contains a different collection of amino acid side chains, including sulfur-containing methionine residues and several aromatic amino acids.
The chemical structure of MOTS-C does not include the modified dimethyltyrosine residue found in SS-31.
Chemical Properties of MOTS-C
| Property | MOTS-C |
|---|---|
| Common name | MOTS-C |
| Full name | Mitochondrial Open Reading Frame of the 12S rRNA-c |
| Amino acid sequence | MRWQEMGYIFYPRKLR |
| Amino acid residues | 16 |
| Molecular formula | C₁₀₁H₁₅₂N₂₈O₂₂S₂ |
| Molecular weight | Approximately 2,174.6 g/mol |
| CAS number | 1627580-64-6 |
| PubChem CID | 146675088 |
| Peptide classification | Mitochondrial-derived peptide |
| Reference C-terminus | Free carboxylic acid |
| Reference N-terminus | Free amino group |
These properties describe the standard free-peptide structure.
The actual chemical composition of a laboratory preparation may also include counterions or other components specified in its analytical documentation.
Researchers can review the PubChem MOTS-C compound record and Orion Peptides’ MOTS-C research reference guide for additional chemical information.
SS-31 vs. MOTS-C: Key Differences at a Glance
The following table summarizes their most important structural and chemical differences.
| Feature | SS-31 | MOTS-C |
|---|---|---|
| Alternative name | Elamipretide | Mitochondrial Open Reading Frame of the 12S rRNA-c |
| Peptide length | 4 amino acids | 16 amino acids |
| Molecular weight | 639.8 g/mol | 2,174.6 g/mol |
| Molecular formula | C₃₂H₄₉N₉O₅ | C₁₀₁H₁₅₂N₂₈O₂₂S₂ |
| Molecular origin | Synthetically designed | Encoded in mitochondrial DNA |
| Peptide family | Szeto-Schiller | Mitochondrial-derived peptide |
| Modified amino acids | Contains D-Arg and Dmt | Standard reference sequence contains conventional amino acids |
| C-terminus | Amidated | Free carboxyl group |
| Cysteine residues | None | None |
| Disulfide bonds | None | None |
| Primary research distinction | Cardiolipin and membrane interactions | Mitochondrial-derived peptide biology |
SS-31 and MOTS-C are not different names for the same compound. They have distinct sequences, structures, and chemical identities.
SS-31 vs. MOTS-C Amino Acid Sequence
The amino acid sequence is one of the clearest ways to distinguish these peptides.
Peptide sequences specify which amino acid residues are present and how they are arranged along the peptide backbone.
Changes in sequence can influence molecular mass, charge distribution, chemical reactivity, and interactions with other molecules.
SS-31 Amino Acid Sequence
The SS-31 sequence is:
D-Arg-Dmt-Lys-Phe-NH₂
Its four residues are:
- D-Arginine
- 2,6-Dimethyltyrosine
- L-Lysine
- L-Phenylalaninamide
The peptide has two noteworthy structural characteristics.
First, the D-arginine residue differs stereochemically from conventional L-arginine.
Second, the 2,6-dimethyltyrosine residue contains methyl substitutions on the aromatic ring.
These modifications are part of the defined SS-31 structure and should be represented correctly in chemical databases and analytical records.
A simple four-letter sequence using standard amino acid codes cannot fully describe these features without additional notation.
MOTS-C Amino Acid Sequence
The MOTS-C sequence is:
MRWQEMGYIFYPRKLR
In three-letter notation:
Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
The peptide contains 16 residues, including:
- Two methionine residues
- Three arginine residues
- Two tyrosine residues
- One tryptophan residue
- One phenylalanine residue
- One lysine residue
- Several additional amino acids
Unlike SS-31, the standard MOTS-C sequence contains no D-arginine or 2,6-dimethyltyrosine modification.
Why Does Sequence Length Matter?
SS-31 contains four amino acid residues, while MOTS-C contains sixteen.
Therefore, MOTS-C has four times as many residues as SS-31.
However, it is not exactly four times heavier.
Molecular weight depends on the identities of the amino acids, their side chains, terminal modifications, and overall chemical composition—not simply the number of residues.
This explains why the parent SS-31 structure has a molecular weight of approximately 639.8 g/mol, while MOTS-C has a molecular weight of approximately 2,174.6 g/mol.
Molecular Weight Differences Between SS-31 and MOTS-C
Molecular weight is an important characteristic in peptide identification.
The two peptides have substantially different masses.
SS-31: Approximately 639.8 g/mol
MOTS-C: Approximately 2,174.6 g/mol
The approximate difference is 1,534.8 g/mol.
MOTS-C therefore has approximately 3.4 times the molecular weight of SS-31.
Why Is Molecular Weight Important in Laboratory Analysis?
Molecular weight can help researchers confirm whether an observed analytical result is consistent with the expected compound.
For example, mass spectrometry measures ions according to their mass-to-charge ratios.
Because SS-31 and MOTS-C have different molecular compositions, their expected mass-spectrometry characteristics differ.
However, the observed signal depends on the charge state and ion type.
Researchers must distinguish average molecular weight from monoisotopic mass and from an observed mass-to-charge ratio.
A molecular-weight match alone does not establish complete peptide identity.
Synthetic Peptide vs. Mitochondrial-Derived Peptide
Another major difference between SS-31 and MOTS-C is their molecular origin.
SS-31: Synthetically Designed Peptide
SS-31 was developed as part of the Szeto-Schiller peptide family.
Its sequence includes residues and structural modifications selected during peptide design.
SS-31 is not encoded as a four-residue peptide by a naturally occurring mitochondrial gene.
Its identity is defined by its synthetic sequence and chemical structure.
MOTS-C: Mitochondrial Genome-Encoded Peptide
MOTS-C was identified through research into short open reading frames associated with mitochondrial DNA.
Its coding sequence is located within the mitochondrial MT-RNR1 region, which is associated with mitochondrial 12S ribosomal RNA.
The peptide was identified in research published in 2015 by Lee and colleagues.
MOTS-C therefore belongs to a different molecular category from SS-31.
An important distinction is that a peptide’s biological coding origin and its manufacturing method are not the same thing.
Commercial MOTS-C research material may be chemically synthesized in a laboratory, even though the naturally occurring peptide sequence is encoded within mitochondrial DNA.
Thus, MOTS-C can be both a mitochondrial genome-encoded peptide by biological origin and a synthetic laboratory compound by manufacturing method.
Comparing Amino Acid Composition and Structural Modifications
SS-31 and MOTS-C also differ in their amino acid chemistry.
Modified Residues in SS-31
SS-31 contains D-arginine and 2,6-dimethyltyrosine.
These residues distinguish it from a peptide composed entirely of conventional L-amino acids.
The D-configuration describes the stereochemistry of the arginine residue.
Dimethyltyrosine contains chemical substitutions not present in ordinary tyrosine.
The SS-31 sequence also terminates in an amide group.
C-terminal amidation is a covalent modification that distinguishes the peptide from its corresponding free-carboxyl form.
Conventional Residues in MOTS-C
The standard MOTS-C peptide consists of 16 conventional amino acid residues.
It contains no cysteine residues, so the standard sequence cannot form an intramolecular disulfide bond through cysteine side chains.
MOTS-C contains two methionine residues, which contribute sulfur atoms to its molecular formula.
Methionine side chains can undergo oxidation under suitable chemical conditions.
This makes methionine-containing regions relevant when analyzing potential peptide oxidation compounds.
Peptide Termini
SS-31 and MOTS-C also differ at their C-termini.
SS-31 has a C-terminal amide.
The standard MOTS-C reference structure has a free C-terminal carboxylic acid.
This distinction matters because terminal groups contribute to molecular formula, charge characteristics, and analytical identity.
How Can Laboratories Distinguish SS-31 From MOTS-C?
Because these peptides differ substantially in sequence and molecular composition, suitable analytical methods can help distinguish them.
High-Performance Liquid Chromatography (HPLC)
HPLC can be used to separate peptide components in a sample.
Retention behavior depends on the chromatographic method, stationary phase, mobile phase, and peptide characteristics.
SS-31 and MOTS-C have different structures and may exhibit different chromatographic behavior.
However, retention time alone should not be considered definitive proof of identity.
Mass Spectrometry (MS)
Mass spectrometry can support identification by measuring characteristic mass-to-charge ratios.
SS-31 and MOTS-C have significantly different molecular masses.
Appropriate mass spectrometry methods can therefore help determine whether an observed sample is consistent with the expected peptide.
Additional fragmentation analysis may provide sequence-related information.
Peptide Sequence Verification
Where required, suitable peptide analytical methods can provide evidence of amino acid sequence or sequence-specific fragments.
This is particularly important when distinguishing peptides with similar masses but different amino acid arrangements.
Assessment of Chemical Modifications
SS-31 contains nonstandard structural features, including D-arginine, dimethyltyrosine, and C-terminal amidation.
The presence and identity of these features may require methods beyond simple mass measurement.
Likewise, the oxidation state of methionine residues may be relevant when assessing MOTS-C preparations.
Certificate of Analysis (COA)
A batch-specific Certificate of Analysis may include identity tests, purity results, and other documented specifications.
Researchers should distinguish between:
- Peptide identity
- Chromatographic purity
- Net peptide content
- Total material mass
- Salt or counterion content
- Additional quality measurements
A reported HPLC purity percentage does not automatically establish every one of these characteristics.
SS-31 and MOTS-C Research Materials at Orion Peptides
Orion Peptides lists both SS-31 and MOTS-C among its laboratory research materials.
Although the compounds are associated with mitochondrial research, they have different chemical identities and should be evaluated separately.
SS-31 Peptide 10mg
Researchers can review SS-31 Peptide 10mg at Orion Peptides for its listed chemical specifications, research-only compound information, and available analytical documentation.
The parent SS-31 sequence contains four residues and has a molecular weight of approximately 639.8 g/mol.
MOTS-C Peptide 10mg
Orion Peptides also lists MOTS-C 10mg for laboratory research.
MOTS-C contains 16 amino acid residues and has a molecular weight of approximately 2,174.6 g/mol.
Researchers can also consult Orion’s MOTS-C Learning Library guide for detailed information about its sequence and molecular characteristics.
Both listings should be evaluated using their own compound specifications and corresponding batch documentation.
Neither compound is intended for human or veterinary consumption.
Frequently Asked Questions
1. What is the main difference between SS-31 and MOTS-C?
SS-31 is a synthetic four-amino-acid peptide, while MOTS-C is a 16-amino-acid peptide encoded by a short open reading frame within mitochondrial DNA.
They have different molecular formulas, sequences, and chemical structures.
2. Are SS-31 and MOTS-C the same peptide?
No. SS-31 and MOTS-C are chemically distinct peptides.
SS-31 is also known as elamipretide, while MOTS-C has its own unique molecular identity and sequence.
3. How many amino acids are in SS-31?
SS-31 contains four amino acid residues and is classified as a tetrapeptide.
4. How many amino acids are in MOTS-C?
MOTS-C contains sixteen amino acid residues.
5. What is the SS-31 peptide sequence?
The sequence is D-Arg-Dmt-Lys-Phe-NH₂.
Dmt represents 2,6-dimethyltyrosine.
6. What is the MOTS-C amino acid sequence?
The standard MOTS-C sequence is MRWQEMGYIFYPRKLR.
7. Which peptide has the higher molecular weight?
MOTS-C has a higher molecular weight.
Its approximate molecular weight is 2,174.6 g/mol, compared with 639.8 g/mol for the SS-31 parent structure.
8. Is SS-31 a mitochondrial-derived peptide?
Not in the genomic sense used to classify MOTS-C.
SS-31 is a synthetically designed peptide investigated in mitochondrial membrane research.
MOTS-C is encoded by a mitochondrial DNA-associated short open reading frame.
9. Do SS-31 and MOTS-C contain disulfide bonds?
Neither standard peptide sequence contains cysteine residues.
Therefore, neither reference structure contains a cysteine-based disulfide bond.
10. What is the difference between SS-31 and elamipretide?
SS-31 and elamipretide refer to the same parent peptide identity.
Elamipretide is the established nonproprietary name, while SS-31 is a research designation.
11. Can mass spectrometry distinguish SS-31 from MOTS-C?
Yes. Suitable mass spectrometry analysis can help distinguish them because their molecular masses and compositions differ significantly.
However, complete identity verification may require additional analytical evidence.
12. Where can researchers find SS-31 and MOTS-C reference materials?
Orion Peptides provides compound listings for SS-31 10mg and MOTS-C 10mg.
Researchers should review the respective compound documentation and batch-specific analytical records.
Conclusion
The comparison of SS-31 vs. MOTS-C demonstrates several important differences between two peptides associated with mitochondrial research.
SS-31 is a synthetically designed tetrapeptide containing four amino acid residues, including D-arginine and 2,6-dimethyltyrosine.
MOTS-C is a mitochondrial genome-encoded peptide consisting of sixteen conventional amino acid residues.
Their molecular weights, chemical formulas, peptide termini, and structural characteristics differ substantially.
Although both are discussed in mitochondrial research literature, they belong to different molecular categories and should not be treated as interchangeable compounds.
For reliable laboratory characterization, researchers should consider peptide sequence, stereochemistry, molecular mass, terminal modifications, and batch-specific analytical documentation.
For further information, explore Orion Peptides’ SS-31 10mg research listing, MOTS-C 10mg compound listing, and SS-31 molecular research guide.
Scientific References
- National Center for Biotechnology Information. PubChem Compound Summary: Elamipretide, CID 11764719. Molecular structure, peptide sequence, formula, and chemical identifiers.
- National Center for Biotechnology Information. PubChem Compound Summary: MOTS-C, CID 146675088. Molecular structure, sequence, and chemical identifiers.
- Lee, C., et al. (2015). The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance. Cell Metabolism, 21(3), 443–454. This study describes the identification of MOTS-C and its mitochondrial genomic origin.
- American Medical Association, United States Adopted Names Council. (2016). Elamipretide — Statement on a Nonproprietary Name. Official nomenclature and chemical identity reference.
- National Center for Biotechnology Information. PubChem Chemical Database. General reference resource for chemical structures and molecular identifiers.
Research Use Only (RUO) Disclaimer
All compounds offered by Orion Peptides, including SS-31 and MOTS-C, are intended strictly for laboratory research, chemical analysis, and scientific investigation.
These materials are not intended for human or veterinary consumption, clinical administration, diagnosis, treatment, cure, or prevention of any disease.
The information provided in this article is for scientific and educational purposes only. Discussions of molecular structures, peptide sequences, published research, or biochemical characteristics do not establish the safety, effectiveness, or suitability of Orion Peptides compounds for clinical use.
Researchers should verify compound identity, chemical form, and batch-specific specifications using appropriate analytical documentation and follow applicable laboratory safety procedures and regulations.
