SS-31 is four residues long, which sounds like the simplest compound in any catalogue. Two of those four are not standard amino acids, and that single fact decides how the molecule has to be documented.
The sequence, and what is unusual in it
The peptide is D-Arg-Dmt-Lys-Phe-NH2. Three things in that short line sit outside ordinary peptide notation.
The first residue is D-arginine, the mirror image of the usual L form. Position two is Dmt, 2',6'-dimethyltyrosine, a tyrosine carrying two extra methyl groups on the ring. The C-terminus is amidated, so the chain ends in an amide and not an acid.
The compound comes from work on mitochondria-targeted peptide antioxidants, a series described by Szeto and Schiller, which is where the SS designation comes from. (Reference: Szeto, 2006) It is also known as elamipretide, and PubChem indexes it under that name.
Why that makes a sequence calculator useless here
Our molecular weight calculator handles the twenty standard amino acids and nothing else. Dmt has no agreed single-letter code, so the calculator rejects the sequence instead of returning a number.
That refusal is the correct behaviour and worth dwelling on. A calculator that silently substituted plain tyrosine would return a mass twenty-eight daltons too low, and that wrong figure would then look like a disagreement with the certificate. A tool that declines to answer is more useful than one that answers approximately.
Chirality compounds the point. D-arginine and L-arginine have identical masses and identical formulas, so no mass measurement distinguishes them. A certificate claiming the D form is making a claim that mass spectrometry cannot check, and the method that can is chiral chromatography. Our note on ipamorelin covers the same issue in a compound that also carries D residues.
Identity on paper
SS-31 is C32H49N9O5, 639.8 g/mol, CAS 736992-21-5. The number passes the check digit and resolves in PubChem to the elamipretide record, whose formula matches. Both steps matter: run the arithmetic with our validator, then look it up and read back the substance it returns.
At 639.8 this is a small molecule by peptide standards, light enough that a mass spectrometer resolves single-atom differences with room to spare. The isotope envelope is narrow, so the distinction between monoisotopic and average mass is smaller here than on a long peptide, though a certificate should still say which it reports.
Two names, one compound
SS-31 and elamipretide are the same molecule under a research designation and a drug name. That is an ordinary situation and not a trap, but it has a practical consequence: a search under one name may return nothing while the other returns a full record. PubChem indexes it as elamipretide.
Our note on CAS numbers covers why a registry identifier beats a name for exactly this reason. One compound can accumulate a code, a generic name, a brand name and several catalogue spellings; the number stays put.
What a certificate should show
The sequence written out with the modifications named, not a bare product code. Purity from RP-HPLC with the conditions. Identity from mass spectrometry, observed against theoretical.
Then the one a short modified peptide needs and a plain one does not: evidence for the stereochemistry. If the document claims a D residue and offers only a mass, it has claimed something it has not measured.
Net peptide content separately from purity, as always, and it bites harder here. On a 640-dalton molecule the counterion from reversed-phase purification is a large share of the weighed powder. Our note on what else is in the vial covers the arithmetic.
What the modifications have in common
All three changes sit where an enzyme would otherwise cut or where the molecule would otherwise be read as ordinary. A D residue is not recognised by the proteases that act on L chains, an amidated terminus removes the free acid those enzymes look for, and a methylated ring changes the local chemistry of position two.
This is the standard grammar of peptide analogue design, the same one behind a D residue in ipamorelin or an acyl group on a GHRH analogue: modify the chain where it is attacked and leave the part that carries the information alone. Recognising the grammar helps when reading an unfamiliar sequence, because the unusual residues are rarely decorative.
Why four residues is still not trivial to make
Three coupling steps is nothing. The difficulty is elsewhere: a non-standard residue has to be sourced or made, a D-amino acid has to stay D through the synthesis, and the amidation has to be complete. Each of those is a place where a batch can be partly wrong while looking entirely normal by purity.
The usual rule of thumb inverts here. On most short peptides purity is easy and identity is the number to read. Here identity is harder than usual too, and the document has to carry more than two figures to settle it.
Storage
A small peptide still degrades by the ordinary routes, which proceed with time and temperature. (Reference: Manning et al., 2010) The amidated terminus is itself hydrolysable, and losing the amide would turn the molecule into the free acid: a change of about one dalton, which is small enough to miss and large enough to matter for identity.
That is a good argument for reading the date on a certificate and not only the figures. Our note on storage sets out the routes.
Research use only
All products sold by Codex Research are strictly for laboratory research and development. They are not for human or animal consumption and are not intended to diagnose, treat, cure, or prevent any disease.
The compound at Codex Research
SS-31, 10 mg per vial · batch-verified, with its certificate of analysis.
Frequently asked questions
What is SS-31?
A four-residue peptide, D-Arg-Dmt-Lys-Phe-NH2, from a series of mitochondria-targeted peptides described by Szeto and Schiller. It is also known as elamipretide.
What does Dmt mean in the sequence?
2',6'-dimethyltyrosine, a tyrosine carrying two extra methyl groups on the ring. It has no agreed single-letter code, which is why sequence calculators cannot handle this compound.
What is the formula and mass of SS-31?
C32H49N9O5, 639.8 g/mol, CAS 736992-21-5. The CAS number passes the check digit and resolves in PubChem to the elamipretide record with a matching formula.
Can mass spectrometry confirm the D-arginine?
No. D and L arginine have identical masses and formulas, so no mass measurement distinguishes them. Chiral chromatography is the method that can.
Why does a calculator refuse this sequence instead of estimating?
Because substituting plain tyrosine for Dmt would return a mass about twenty-eight daltons too low, and that wrong figure would then look like a disagreement with the certificate. Declining is more useful than answering approximately.
Is a short peptide easier to make correctly?
Fewer coupling steps, yes. But a non-standard residue has to be sourced, a D-amino acid has to stay D through synthesis, and the amidation has to be complete. Each is a place a batch can be partly wrong while looking normal by purity.
References
- Szeto, H.H. (2006). Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. The AAPS Journal, 8(3), E521-E531.
- Elamipretide compound summary (CID 11764719). PubChem, National Library of Medicine.
- Merrifield, R.B. (1963). Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. Journal of the American Chemical Society, 85(14), 2149-2154.
- Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F., & Whitehouse, C.M. (1989). Electrospray ionization for mass spectrometry of large biomolecules. Science, 246(4926), 64-71.
- Manning, M.C., Chou, D.K., Murphy, B.M., Payne, R.W., & Katayama, D.S. (2010). Stability of protein pharmaceuticals: an update. Pharmaceutical Research, 27(4), 544-575.
- Dong, M.W. (2006). Modern HPLC for Practicing Scientists. Wiley.