Unlike oxidation or deamidation, aggregation is a physical degradation: no bonds are broken, but the molecules stick to each other through their hydrophobic regions. Some peptides are especially prone to it, such as native human amylin, which forms amyloid fibrils, or lipidated peptides.
It is promoted by high concentrations, a pH close to the isoelectric point, shaking (which creates air-liquid interfaces), freeze-thaw cycles and heat. A related phenomenon is adsorption: at very low concentrations, part of the peptide sticks to glass or plastic.
The visible sign is a cloudy solution, with particles or strands. A correctly reconstituted peptide solution should be clear.
Aggregates not only reduce the amount of active peptide: in biological systems they can increase immunogenicity. That is why the rule of dissolving by gentle swirling, without shaking, has a solid basis.
Related terms
Learn it in depth at the Peptide University
- Physical degradation: aggregation and adsorption · Module 11
- Lyophilization and excipients · Module 11
- Amylin, the oral route and the next generation · Module 3
- Related impurities and counterions · Module 7
- The lyophilized form and its diluents · Module 8
Definition for educational and scientific purposes. It is not medical advice or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).