Modifications of therapeutic proteins: challenges and prospects
Modifications of therapeutic proteins: challenges and prospects
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DOI：
10.1007/s10616-007-9075-2
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发表时间：
2007-04-01
期刊：
影响因子：
2.2
通讯作者：
Jenkins, Nigel
中科院分区：
文献类型：
--
作者：
Jenkins, Nigel
治疗性蛋白质的生产是制药业增长最快的部门之一。然而，大多数用于药物治疗的蛋白质都需要复杂的翻译后修饰，以实现有效的分泌、药物疗效和稳定性。常见的蛋白质修饰包括可变的糖基化、错误折叠和聚集、蛋氨酸的氧化、天冬酰胺和谷氨酰胺的脱酰胺以及蛋白质的降解。这些修改不仅对准确和一致的生物处理提出了挑战，而且可能会对患者产生后果，因为不正确的修改或聚集可能会导致对蛋白质治疗的免疫反应。这篇综述提供了为应对这些挑战而设计的分析和预防性进展的例子，并对进一步的进展如何提高重组蛋白的效率和安全性提供了见解。
The production of therapeutic proteins is one of the fastest growing sectors of the pharmaceutical industry. However, most proteins used in drug therapy require complex post-translational modifications for efficient secretion, drug efficacy and stability. Common protein modifications include variable glycosylation, misfolding and aggregation, oxidation of methionine, deamidation of asparagine and glutamine, and proteolysis. These modifications not only pose challenges for accurate and consistent bioprocessing, but also may have consequences for the patient in that incorrect modifications or aggregation may lead to an immune response to the protein therapeutic. This review provides examples of analytical and preventative advances that have been devised to meet these challenges, and insights into how further advances can improve the efficiency and safety in manufacturing recombinant proteins.