Methionine oxidation (revision 7)
Old revision·02:23, 27 Jan 2025·Ref_Desk_Ron
| Methionine oxidation | |
|---|---|
| Residue affected | Methionine; cysteine and tryptophan by related routes |
| Mass change | +16 Da (sulfoxide); +32 Da (sulfone) |
| Promoted by | Peroxides, trace metals, light, dissolved oxygen |
| Topic infobox · conventions | |
Methionine oxidation converts the thioether side chain of methionine to a sulfoxide, adding 16 daltons, and on further oxidation to a sulfone, adding 32. It is one of the most common oxidative degradation routes in peptides and is readily detected by mass spectrometry because the mass shift is large.[1]
Oxidation is promoted by dissolved oxygen, by trace transition metals, by peroxide impurities in excipients, and by light. Unlike deamidation, which proceeds spontaneously in clean aqueous solution, oxidation generally requires an oxidant, and controlling the oxidant is therefore an effective control strategy.[2]
The consequence for activity depends on where the methionine sits. A surface methionine remote from the binding region may be oxidised with little effect; one within the receptor-contact region can substantially reduce potency.[1]
Chemistry and promoters
[edit]The sulfur of methionine is readily oxidised by two-electron oxidants such as hydrogen peroxide to the sulfoxide, a reaction that is fast and essentially irreversible under ordinary conditions. Further oxidation to the sulfone requires more forcing conditions and is less commonly observed in practice.[1]
Metal-catalysed oxidation is the more insidious route. Trace iron or copper, in the presence of oxygen and a reducing agent, generates reactive species locally at metal-binding sites, so oxidation can be site-specific rather than uniform. Chelating agents in formulations exist largely to suppress this.
Peroxide contamination of excipients — polysorbates in particular are prone to peroxide formation on storage — is a recognised source in formulated products. For research peptides supplied as unformulated lyophilisates the more likely sources are the drying process, container headspace and light exposure.[2]