Degradation

Degradation is the umbrella term for every process through which a peptide stops being the molecule it is supposed to be. It helps to divide these processes into chemical routes, which change covalent structure, and physical routes, which change the state of the material while leaving its chemistry intact.

Key pathways

In hydrolysis the peptide bond itself is split; water, heat and pH extremes speed it up, and Asp-Pro sequences are especially vulnerable. Deamidation turns asparagine or glutamine into the corresponding acid through a succinimide intermediate, adds 1 Da and frequently leaves an isoaspartate that changes conformation; Asn-Gly motifs are the textbook weak point. Oxidation adds 16 Da for each oxygen taken up at methionine, cysteine or tryptophan. Disulfide scrambling rearranges which cysteines are paired in cyclised sequences. On the physical side, aggregation pushes dissolved chains into oligomers and visible particles, and adsorption simply loses peptide to the walls of the container.

Detecting it

Every route leaves a characteristic trace. On HPLC you see additional peaks or a displaced main peak; mass spectrometry reveals the diagnostic mass change — +16 for oxidation, +1 for deamidation, a reduced mass after cleavage. A degraded lot can look perfectly fine to the eye, so how it was stored and an up-to-date certificate of analysis tell you far more than its appearance. See the storage guide.

Related terms

stability · freeze–thaw