期刊
PHARMACEUTICS
卷 13, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics13111853
关键词
pharmaceutical proteins; liquid formulation; glycerol; protein stability; chemical degradation; chemical stability; protein conformation
资金
- Swedish Governmental Agency for Innovation System (VINNOVA) [2017-02155]
- European Union Horizon 2020 research and innovation programme (EUSMI) [731019]
- Lund University's APC fund
- Forte [2017-02155] Funding Source: Forte
- Vinnova [2017-02155] Funding Source: Vinnova
The addition of glycerol to protein solutions can hinder aggregation and denaturation, but may not always prevent chemical degradation reactions. Glycerol-induced conformational changes in proteins can lead to a more compact and chemically stable state, providing protection against deamidation, isomerisation, and hydrolysis. Understanding the influence of glycerol on protein stability and conformational changes is key to improving the functionality of pharmaceutical proteins.
The addition of glycerol to protein solutions is often used to hinder the aggregation and denaturation of proteins. However, it is not a generalised practice against chemical degradation reactions. The chemical degradation of proteins, such as deamidation and isomerisation, is an important deteriorative mechanism that leads to a loss of functionality of pharmaceutical proteins. Here, the influence of glycerol on the chemical degradation of a protein and its correlation to glycerol-induced conformational changes is presented. The time-dependent chemical degradation of a pharmaceutical protein, GA-Z, in the absence and presence of glycerol was investigated in a stability study. The effect of glycerol on protein conformation and oligomerisation was characterised using asymmetric field-flow fractionation and small-angle neutron scattering in a wide glycerol concentration range of 0-90% v/ v. The results from the stability study were connected to the observed glycerol-induced conformational changes in the protein. A correlation between protein conformation and the protective effect of glycerol against the degradation reactions deamidation, isomerisation, and hydrolysis was found. The study reveals that glycerol induces conformational changes of the protein, which favour a more compact and chemically stable state. It is also shown that the conformation can be changed by other system properties, e.g., protein concentration, leading to increased chemical stability.
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