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What are Potential Causes of Polypeptide Instability?

Deamidation: non-enzymatic catalyzed deamidation reaction, which is related to environmental conditions and polypeptide structure  

Oxidized: Peroxide contamination, or spontaneous oxidation, Met, Cys and His, Trp, Tyr are the most susceptible to oxidation. Oxygen partial pressure, temperature, and buffer solution also have an effect on oxidation.  

Hydrolysis: The peptide bond is easily broken by hydrolysis. The peptide bond formed by Asp is more easily broken than other peptide bonds, especially Asp-Pro and Asp-Gly peptide bonds  

Disulfide bond mismatch  

Racemization: All amino acid residues except Gly. All carbon atoms are chiral, and are susceptible to base-catalyzed racemization; Asp residues are most easily eliminated;

β-elimination: β-elimination refers to the elimination of groups on the β carbon atom of residue amino acid Residues such as Cys, Ser, Thr and Phe can be solved by purging-elimination, which is easy to occur at basic pH value.  

Denaturation, adsorption, aggregation or precipitation: such as IL-13, IL-2 and some peptides we are doing are easy to adsorb