The instability of peptide is one of the main problems in the study of its preparation, and there are many reasons for it. However, there are not many major causes of instability for any one peptide. A detailed study of the influence of external conditions (such as PH, temperature, light, oxygen concentration, etc.) on the stability of peptides is helpful for the design of rational formulations. Although the mechanism by which additives stabilize peptides is not well understood, the use of additives is still one of the main means to improve the stability of peptide preparations. The application of CD, DSC and other analytical means can help to quickly screen suitable additives.

Causes of peptide instability

1. Deamidation reaction： In the deacylation reaction, Asn/Gln residues hydrolyze to form Asp/Glu. The conduct of non-enzyme-catalyzed deamidation reactions. The amide groups in the ASN-GLY-structure are more easily hydrolyzed, and the amide groups located on the molecular surface are more easily hydrolyzed than the amide groups in the molecular interior.

2. There are two main reasons for the easy oxidation of peptide solution: one is the pollution of peroxide in the solution, and the other is the spontaneous oxidation of peptide. Among all amino acid residues, Met, Cys and His, Trp and Tyr are the most easily oxidized. Oxygen partial pressure, temperature and buffer solution also affect oxidation.

3. Peptide bonds : in hydrolyzed peptides are easily hydrolyzed and broken. Peptide bonds formed by Asp are more easily broken than other peptide bonds, especially the ASP-Pro and ASP-GLY peptide bonds.

4. Formation of incorrect disulfide bonds ：Exchange between disulfide bonds or between disulfide bonds and sulfhydryl groups can form incorrect disulfide bonds, resulting in tertiary structure changes and loss of activity.

5.β-elimination：β-elimination refers to the elimination of groups on the β-carbon atom in amino acid residues. Cys, Ser, Thr, Phe, Tyr and other residues can be degraded by β-elimination. β-elimination is easy to occur at alkaline PH, and temperature and metal ions also affect it.

6.Denaturation, adsorption, aggregation or precipitation denaturation is generally associated with the destruction of the tertiary structure and the secondary structure：In the denatured state, peptides are often more prone to chemical reactions, and their activity is difficult to recover. In the process of denaturation of peptide, the intermediate is formed first. Usually, the solubility of the intermediate is low, and it is easy to aggregate, forming aggregates, and then forming visible precipitation.

Surface adsorption of proteins is another headache encountered in the process of storage and use, such as riL-2 will adsorb on the surface of the pipeline during the infusion of march music, resulting in loss of activity.

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