去酰胺
降级(电信)
化学
离子强度
蛋白质降解
蛋白质聚集
蛋白质稳定性
色谱法
生物物理学
生物化学
计算机科学
有机化学
电信
生物
酶
水溶液
作者
Cleland Jl,Powell Mf,Shire Sj
出处
期刊:PubMed
日期:1993-01-01
卷期号:10 (4): 307-77
被引量:137
摘要
The biochemical literature has been surveyed to present an overview of the three most common protein degradation pathways: protein aggregation, deamidation, and oxidation. The mechanisms for each of these degradation routes are discussed with particular attention given to the effect of formulation conditions such as pH, ionic strength, temperature, and buffer composition. Strategies to reduce protein degradation are also discussed. These strategies are based on an understanding of the degradation mechanisms and the effect of changes in the storage conditions and formulation components on the degradation. The effects of each of the degradation routes on pharmaceutically relevant properties such as biological activity, metabolic half-life, and immunogenicity are summarized. Predicting a priori the alteration of pharmaceutical properties caused by the three degradation routes is difficult, and must be determined on a case-by-case basis for each protein. The difficulty in predicting the effect of degradation and analyzing the temperature dependence of reaction rates in proteins results in longer development times for protein formulations than for small molecule formulations. Although the use of accelerated stability to predict protein shelf life is difficult, conditions are discussed whereby the Arrhenius equation can be used to shorten formulation development time.
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