Peptide Oxidation vs Hydrolysis: Key Differences in Degradation Pathways
Oxidation and hydrolysis are the two dominant degradation routes for peptides — but they happen for completely different reasons and demand different countermeasures.
When a peptide degrades, it rarely degrades in just one way. Oxidation and hydrolysis are the two heaviest contributors, and recognizing which one is dominant in your sample is the first step toward fixing it.
Oxidation: an electron problem
Oxidation is driven by reactive oxygen species attacking sulfur-containing residues or aromatic side chains. It is accelerated by light, heat, transition metal contamination, and dissolved oxygen.
Hydrolysis: a water problem
Hydrolysis cleaves the peptide backbone at amide bonds, with rates strongly dependent on pH and temperature. Asp-Pro and Asn-Gly junctions are notoriously labile.
Diagnosing in the lab
Mass spectrometry will show characteristic +16 Da shifts for oxidation and fragment ladders for hydrolysis. Knowing which signature appears tells you whether to control oxygen or pH first.
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