Review: Why is arginine effective in suppressing aggregation?

Review: Why is arginine effective in suppressing aggregation?
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DOI:
10.2174/0929866054696109
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发表时间:
2005-09
影响因子:
1.6
通讯作者:
K. Tsumoto;D. Ejima;Y. Kita;T. Arakawa
K. Tsumoto;D. Ejima;Y. Kita;T. Arakawa
中科院分区:
生物学4区
文献类型:
--
作者:
K. Tsumoto;D. Ejima;Y. Kita;T. Arakawa

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精氨酸在蛋白质生产中有着广泛的应用。精氨酸多年来一直被用来帮助蛋白质重折叠。这种效应归因于蛋白质重折叠过程中精氨酸对折叠中间体的聚集抑制。最近,我们观察到精氨酸促进 Protein-A 层析过程中抗体的洗脱,并溶解包涵体中的不溶性蛋白质,这两者都可以归因于蛋白质-蛋白质相互作用的减弱。为了了解精氨酸为何能有效减少蛋白质-蛋白质相互作用和抑制聚集,研究人员检查了精氨酸对纯蛋白质稳定性和溶解度的影响,结果表明精氨酸不是蛋白质稳定剂,而是聚集抑制剂。然而,到目前为止,还没有提出关于精氨酸为何抑制蛋白质聚集的解释。这篇综述解决了这个问题,然后试图显示精氨酸和强变性剂(也称为聚集抑制剂)之间的差异。
Arginine is finding a wide range of applications in production of proteins. Arginine has been used for many years to assist protein refolding. This effect was ascribed to aggregation suppression by arginine of folding intermediates during protein refolding. Recently, we have observed that arginine facilitates elution of antibodies during Protein-A chromatography and solubilizes insoluble proteins from inclusion bodies, which both can be ascribed to weakening of protein-protein interactions. In order to gain understanding on why arginine is effective in reducing protein-protein interactions and suppressing aggregation, the effects of arginine on stability and solubility of pure proteins have been examined, which showed that arginine is not a protein-stabilizer, but is an aggregation suppressor. However, there is no explanation proposed so far on why arginine suppresses aggregation of proteins. This review addresses such question and then attempts to show differences between arginine and strong denaturants, which are also known as an aggregation suppressor.