What Actually Degrades a Peptide
Heat, light, oxidation, hydrolysis and freeze-thaw attack peptides by different routes. Which matters depends on the sequence.
Lyophilised is stable; in solution is not
The single largest factor in peptide stability is whether water is present. Freeze-dried powder with low residual moisture is stable for long periods at refrigeration temperature, and often for a considerable time at room temperature. The same peptide in solution is a different proposition entirely, because water enables the hydrolysis and deamidation reactions that break peptides down. This is why the in-use window after reconstitution is measured in weeks while the lyophilised shelf life is measured in years.
Deamidation targets specific residues
Asparagine and glutamine residues convert to aspartate and glutamate over time, particularly at neutral to alkaline pH. The product is a peptide of the correct length with a changed residue, which may be inactive and will not necessarily be obvious on a routine purity check. Sequences rich in asparagine are inherently more susceptible, which is why stability varies between peptides rather than being a single universal figure.
Oxidation targets others
Methionine, cysteine and tryptophan residues oxidise on exposure to air and light. Cysteine oxidation additionally causes dimerisation through disulfide bond formation, producing a molecule of double the mass. This is why vials should be closed promptly and why amber or foil-protected packaging is used for susceptible sequences rather than as a general precaution.
Freeze-thaw is mechanical damage
Repeated freezing and thawing damages peptides through ice crystal formation and through the concentration of solutes that occurs as water freezes out. The damage is cumulative and it is why the advice is to aliquot a reconstituted vial once rather than to freeze and thaw the same vial repeatedly. LL-37 and IGF-1 are frequently singled out in the literature as particularly intolerant.
Adsorption quietly removes peptide
Peptides bind to glass and plastic surfaces. At low concentrations a measurable proportion of the peptide can be lost to the walls of the vial and the syringe rather than to any chemical change. This is why some products specify a carrier protein or a particular container, and why very dilute preparations lose more than the arithmetic predicts.
Temperature excursions are cumulative
Stability is not a switch that flips at a threshold. Degradation rates roughly follow Arrhenius behaviour, meaning each excursion contributes in proportion to how warm and how long. A package that sat warm for a day has used part of the product's stability budget even if it looks perfect, which is the argument for opening and refrigerating on arrival rather than when convenient.