Degradation is the collective term for any process by which a peptide ceases to be the intended molecule. It is worth separating into chemical routes, which alter covalent structure, and physical ones, which alter state without changing chemistry.
The main degradation routes
Hydrolysis cleaves the peptide bond itself, accelerated by water, heat and extremes of pH, and Asp-Pro sequences are notably labile. Deamidation converts asparagine or glutamine to their acid forms via a succinimide intermediate, adding 1 Da and often creating an isoaspartate that alters conformation; Asn-Gly motifs are the classic hotspot. Oxidation adds 16 Da per oxygen at methionine, cysteine or tryptophan. Disulfide scrambling reshuffles cysteine pairings in cyclised sequences. Physically, aggregation drives soluble chains into oligomers and visible particulates, and adsorption simply removes peptide onto container walls.
Why it matters
Each route has a signature. HPLC shows new peaks or a shifted main peak, while mass spectrometry shows the tell-tale mass shift — plus 16 for oxidation, plus 1 for deamidation, a lower mass for cleavage. A degraded lot may still look pristine, which is why storage conditions and a current certificate of analysis carry more weight than appearance. See the storage guide.