Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada N2L3G1.
Biotechnol Adv. 2011 Nov-Dec;29(6):923-9. doi: 10.1016/j.biotechadv.2011.07.013. Epub 2011 Jul 29.
Therapeutic proteins require correct disulfide bond formation for biological activity and stability. This makes their manufacturing and storage inherently challenging since disulfide bonds can be aberrantly formed and/or undergo significant structural changes. In this paper the mechanisms of disulfide bond formation and scrambling are reviewed, with a focus on their impact on the biological activity and storage stability of recombinant proteins. After assessing the research progress in detecting disulfide bond scrambling, strategies for preventing this phenomenon are proposed.
治疗性蛋白需要正确的二硫键形成才能保持生物活性和稳定性。这使得它们的制造和储存具有内在的挑战性，因为二硫键可能会异常形成和/或发生重大结构变化。本文回顾了二硫键形成和重排的机制，并重点讨论了它们对重组蛋白生物活性和储存稳定性的影响。在评估了检测二硫键重排的研究进展后，提出了预防这种现象的策略。
