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Comparison of accompanying proteins in different therapeutic human serum albumin preparations.
Biologicals ( IF 1.7 ) Pub Date : 2020-01-21 , DOI: 10.1016/j.biologicals.2020.01.003
Stefan Mikkat 1 , Adrian Dominik 2 , Jan Stange 3 , Martin Eggert 2
Affiliation  

Pharmaceutical human serum albumin products are manufactured from donated human plasma and may contain up to 5% accompanying non-albumin proteins. It has been reported that albumin preparations manufactured by different pharmaceutical companies differed in the degree of posttranslational modifications, the redox state as well as antioxidant properties of albumin, whereas the composition of the accompanying proteins has never been comparatively analyzed. In this study, a non-targeted mass spectrometric approach was used for label-free quantification and comparison of different pharmaceutical albumin preparations. Haptoglobin and a few other proteins accounted for approximately 80% of the accompanying proteins in all products tested. Low abundance proteins were enriched by means of a combinatorial peptide ligand library (ProteoMiner, Bio-Rad). Significant differences between the amounts of several mainly low abundance proteins, such as complement factors, were observed indicating differences in the manufacturing processes of the pharmaceutical companies. The removal of the stabilizers octanoate and N-acetyltryptophan from albumin solutions using the charcoal-based Hepalbin adsorbent simultaneously reduced the accompanying proteins. For therapy evaluation of albumin preparations, the variable composition of the accompanying proteins in different albumin products should be taken into account in addition to the known heterogeneity of the albumin protein itself.



中文翻译:

不同治疗性人类血清白蛋白制剂中伴随蛋白的比较。

药用人血清白蛋白产品是从捐赠的人血浆中生产的,可能含有多达5%的伴随非白蛋白蛋白。据报道,由不同制药公司生产的白蛋白制剂在翻译后修饰的程度,白蛋白的氧化还原状态以及抗氧化特性方面有所不同,而从未对蛋白质的组成进行比较分析。在这项研究中,非目标质谱方法用于无标记的定量和不同药物白蛋白制剂的比较。在所有测试的产品中,结合珠蛋白和其他一些蛋白质约占伴随蛋白质的80%。低丰度蛋白质通过组合肽配体库(ProteoMiner,Bio-Rad)富集。观察到几种主要的低丰度蛋白质(例如补体因子)的数量之间存在显着差异,表明制药公司的生产工艺存在差异。使用基于木炭的Hepalbin吸附剂从白蛋白溶液中去除稳定剂辛酸酯和N-乙酰基色氨酸同时还原了伴随的蛋白质。为了评估白蛋白制剂的治疗效果,除了已知的白蛋白蛋白本身的异质性外,还应考虑不同白蛋白产品中伴随蛋白的可变组成。使用基于木炭的Hepalbin吸附剂从白蛋白溶液中去除稳定剂辛酸酯和N-乙酰基色氨酸同时还原了伴随的蛋白质。为了评估白蛋白制剂的治疗效果,除了已知的白蛋白蛋白本身的异质性外,还应考虑不同白蛋白产品中伴随蛋白的可变组成。使用基于木炭的Hepalbin吸附剂从白蛋白溶液中去除稳定剂辛酸酯和N-乙酰基色氨酸同时还原了伴随的蛋白质。为了评估白蛋白制剂的治疗效果,除了已知的白蛋白蛋白本身的异质性外,还应考虑不同白蛋白产品中伴随蛋白的可变组成。

更新日期:2020-01-21
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