基于热稳定的伴侣的多生物合成:恩福维尔提德模型产品质量和与协议相关的杂质
Vladimir Zenin1, Andrey Tsedilin1, Maria Yurkova1
1Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russian Federation.
PloS one
|June 8, 2023
概括
大型生物合成为Enfuvirtide提供了一种新的生产方法,Enfuvirtide是艾滋病毒治疗的关键. 虽然符合质量标准,但与化学合成Enfuvirtide相比,观察到治疗活性的微小差异.
科学领域:
- 生物技术是生物技术.
- 制药合成 制药合成
- 生物化学 生物化学
背景情况:
- 像Enfuvirtide这样的大型治疗对于艾滋病毒治疗至关重要.
- 传统的化学合成对大型的生产提出了挑战.
- 生物技术方法提供了替代的制造途径.
研究的目的:
- 为了评估生物合成产生的恩福维的质量和杂质概况.
- 为了比较生物合成Enfuvirtide和化学合成Enfuvirtide的特征.
- 评估使用基于热稳定的伴侣系统用于大型制造的可行性.
主要方法:
- 基于热稳定的伴侣生物合成系统.
- 液体染色学-质谱学 (LC-MS) 用于杂质分析.
- 循环二重化 (CD) 光谱用于结构比较.
- 使用MT-4细胞进行HIV感染抑制测定.
主要成果:
- 生物合成Enfuvirtide符合质量要求,具有较低的内毒素 (1.06 EU/mg) 和宿主细胞蛋白 (HCP) 水平 (5.58 ppm).
- 通过LC-MS分析,确定和量化了与工艺相关的杂质.
- 治疗活性 (IC50) 显示出差异 (0.0453μM与0.0180μM),归因于非化C端.
结论:
- 类生物合成是一种可行的替代方法,可以生产像Enfuvirtide这样的治疗性.
- 微小的结构差异可能会影响生物活动,需要进一步调查.
- 开发的系统显示了大规模治疗性制造的潜力.
相关概念视频
Molecular Chaperones and Protein Folding
18.1K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
18.1K
Bacterial Protein Maturation
40
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
40


