CIBER de Bioingeniería, Biomateriales y Nanomedicina, Bellaterra, 08193 Barcelona, Spain.
Curr Pharm Biotechnol. 2011 Oct;12(10):1530-6. doi: 10.2174/138920111798357339.
Production of protein-based pharmaceuticals is a major issue in conventional pharmacology, biomedicine and nanomedicine. Being mostly obtained by genetic engineering, the quality and activity of protein drugs is a steady matter of concern. Although the physiology of the host recombinant cells, mostly mammalian and microbial, is progressively understood, the complexity of the cellular quality control systems escapes rational protein and process engineering, and recombinant proteins are often unstable, aggregate and/or do not reach the fully native conformation compatible with proper biological activity. In this review, we summarize the main biological aspects of protein folding and misfolding, mainly focusing in microbial cells, the newest insights in the biological control of protein quality and the main and analytical approaches that are suitable for the fast evaluation of the conformational quality and aggregation of recombinant drugs, even if showing apparent solubility.
蛋白质类药物的生产是传统药理学、生物医学和纳米医学的一个主要问题。这些药物主要通过基因工程获得，其质量和活性一直是人们关注的焦点。尽管宿主重组细胞（主要是哺乳动物和微生物）的生理学逐渐被人们所了解，但细胞质量控制系统的复杂性使得理性的蛋白质和工艺工程难以实现，而且重组蛋白往往不稳定、聚集和/或无法达到与适当生物活性兼容的完全天然构象。在这篇综述中，我们总结了蛋白质折叠和错误折叠的主要生物学方面，主要集中在微生物细胞上，以及对蛋白质质量的生物学控制的最新见解，以及适用于快速评估重组药物构象质量和聚集的主要和分析方法，即使它们表现出明显的溶解度。
