Disulfide bonds in peptides.
When two cysteine side chains meet, their sulfur atoms can bond to each other, tying the chain into a loop or linking two chains together. That single S–S bond shapes hormones such as oxytocin and vasopressin. Here is how it forms, what it does to the mass and the absorbance, real examples, and how a lab confirms which cysteines are paired.
Two thiols, one bond.
Cysteine carries a thiol (SH) group. Two thiols can be oxidized to a disulfide, R–S–S–R, losing two hydrogen atoms in the process. The bonded pair is called cystine. Inside one chain the bond closes a ring (intramolecular); between two chains it links them (intermolecular), as in insulin's A and B chains or in glutathione's oxidized dimer.
A disulfide is a covalent bond, but a reducible one: reducing agents such as DTT or TCEP break it back into two thiols, which is how labs open rings to check them.
Shape, mass, absorbance.
- Shape. A disulfide holds two parts of the chain together, so a peptide with one or more of them keeps a defined fold. Disulfide-rich peptides from venoms and plants are among the most stable peptides known.
- Mass. Each disulfide lowers the mass by two hydrogens: 2.016 g/mol average, 2.0157 Da monoisotopic. A peptide with two free cysteines that has formed its ring weighs 2.02 less than the reduced chain.
- Absorbance. Cystine absorbs weakly at 280 nm, about 125 M-1 cm-1 per bond (Pace, 1995), a small addition to the tryptophan and tyrosine signal; the extinction coefficient calculator has a box for it.
Disulfides in familiar sequences.
| Compound | Disulfide pattern | Residues | Formula | MW (g/mol) | PubChem CID |
|---|---|---|---|---|---|
| Oxytocin | Cys1 to Cys6, a six-residue ring | 9 | C43H66N12O12S2 | 1007.2 | 439302 |
| Vasopressin (argipressin) | Cys1 to Cys6, a six-residue ring | 9 | C46H65N15O12S2 | 1084.2 | 644077 |
| Octreotide | Cys2 to Cys7 | 8 | C49H66N10O10S2 | 1019.2 | 448601 |
| Linaclotide | three disulfides | 14 | C59H79N15O21S6 | 1526.8 | 16158208 |
| Glutathione (reduced) | free thiol; two molecules join into a disulfide dimer when oxidized | 3 | C10H17N3O6S | 307.3 | 124886 |
Formulas and weights from PubChem. Apart from glutathione, these are reference compounds for the chemistry, not Helion products.
Which cysteine bonds to which.
With two cysteines there is only one way to pair them, but with four there are three and with six there are fifteen, so labs confirm the pattern. The usual workflow compares the intact mass with the mass after reduction (the difference counts the bonds), then digests the unreduced peptide with an enzyme and identifies the fragments still held together by each S–S bond by mass spectrometry. In synthesis, chemists protect cysteine pairs with different groups and close the rings one at a time to force the right pairing. Wrongly paired isomers usually elute as separate HPLC peaks; the chromatogram guide and the mass spectrometry guide cover both methods.
Peptides with free cysteines can also pair up with each other on standing in air, forming dimers that show at roughly twice the mass minus 2.02, which is why cysteine-containing peptides are analysed and stored with that in mind.
No cysteines in the catalog.
None of the compounds on Helion's compound pages contains cysteine: BPC-157, TB-500, MOTS-c, SS-31, CJC-1295, ipamorelin, tesamorelin and GHK are all cysteine-free chains, so none has a disulfide bond to check. Each compound page lists its sequence, and the sequence converter counts residues, cysteines included, for any sequence you paste.
Specs and storage by compound.
Questions (6)
What is a disulfide bond in a peptide?
A covalent S-S bond between the side chains of two cysteines, formed by oxidation. The bonded pair is called cystine, and it ties two parts of a chain, or two chains, together.
How does a disulfide bond change peptide mass?
Each disulfide removes two hydrogen atoms, lowering the mass by about 2.02 g/mol (2.0157 Da monoisotopic) compared with the reduced chain.
Does oxytocin have a disulfide bond?
Yes, one: between cysteine 1 and cysteine 6, which closes a six-residue ring. Vasopressin has the same pattern.
How are disulfide bonds broken in the lab?
With reducing agents such as DTT or TCEP, which turn the disulfide back into two thiols. Comparing the mass before and after reduction counts the bonds.
What is the difference between cysteine and cystine?
Cysteine is the single amino acid with a free thiol group; cystine is two cysteines joined by a disulfide bond.
Do any Helion compounds contain disulfide bonds?
No. None of the compounds on Helion's compound pages contains cysteine, so none has a disulfide.
Published studies (4)
- Cellular disulfide bond formation in bioactive peptides and proteins
- Native and Engineered Cyclic Disulfide-Rich Peptides as Drug Leads
- Biomimetic Folding Strategies for Chemical Synthesis of Disulfide-Bonded Peptides and Proteins
- How to measure and predict the molar absorption coefficient of a protein
Citations from PubMed for reference. They describe the compound in the literature, not any Helion lot, and nothing here is guidance on use.