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设计,表达和结合相互作用研究重组工程IL-6R的研究

Elham Mehdizadeh Marzenaki¹, Mojgan Bandehpour^2,3, Adel Haghighi⁴

¹Department of Molecular Medicine, School of Advanced Technologies, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Iranian journal of pharmaceutical research : IJPR

|December 8, 2025

概括

改造的干白素-6受体 (IL-6R) 片段被设计为减少与糖蛋白130 (gp130) 的结合. 这种工程蛋白显示出作为一种具有成本效益的治疗方法来治疗IL-6相关疾病的潜力.

科学领域:

生物化学生物化学
分子生物学分子生物学
结构生物学结构生物学

背景情况:

溶性互白素-6受体 (IL-6R) 转信号与慢性炎症疾病,自身免疫疾病和癌症有关.
针对IL-6R-gp130相互作用是管理这些IL-6介导病理的一个关键策略.

研究的目的:

通过计算模型和工程设计IL-6R (残留物121-300) 的片段,以减少其与糖蛋白130 (gp130) 的结合亲和力.
为潜在的治疗应用表达和描述工程IL-6R片段 (seIL-6R).

主要方法:

使用AlphaFold和ClusPro进行对接模拟的蛋白质工程和分子建模.
在中国仓鼠卵巢 (CHO) -K1细胞中,seIL-6R的重组表达.
生物化学和生物物理特征,包括西方模糊和里埃变换红外光谱 (FTIR).

主要成果:

改造的seIL-6R碎片表现出更好的稳定性,可溶性和降低的分子量 (20.6 kDa).
分子对接预测了seIL-6R和gp130.0之间的结合相互作用减少.
西部涂抹证实了成功的重组蛋白表达,FTIR分析证实了二次结构的保存.

结论:

改造的seIL-6R蛋白显示出有利的物理化学特性,并减少了与gp130.0.的结合.
这种工程蛋白质代表了进一步开发作为治疗IL-6驱动疾病的治疗剂的有希望的候选人.

关键词:

自免疫性疾病自免疫性疾病在IL-6的研究中,IL-6被认为是IL-6的基因.分子对接分子对接再组合蛋白的表达方式

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