将转变稳定性转化为类似病毒的粒子以实现触发解离
Caleb A Starr1, Smita Nair1, Sheng-Yuan Huang2
1Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana 47405, United States.
Journal of the American Chemical Society
|January 18, 2023
概括
研究人员设计了一种乙型肝炎病毒 (HBV) 病毒样粒子 (VLP) 传递系统. 这触发了使用化学生物学的VLP拆卸,使控制的货物释放用于治疗应用.
科学领域:
- 生物化学
- 化学生物学
- 材料科学
背景情况:
- 病毒样颗粒 (VLP) 是药物输送的有希望的,但需要触发货物释放机制.
- 乙型肝炎病毒 (HBV) 囊蛋白 (Cp) 自组合成VLP,提供潜在的发展平台.
研究的目的:
- 设计一种化学触发的HBVVLP拆解机制.
- 创建一个超稳定的VLP系统以响应特定的环境线索释放货物.
主要方法:
- 用两种囊蛋白 (C150,C124) 重新设计的HBV Cp用于交叉链接和化学修饰.
- 使用C124的光体组装120度VLP并诱导转移稳定性.
- 使用FRET,尺寸排除色谱和电阻脉冲传感器来监测VLP解离.
- 采用数学建模来理解拆解动力学和核化过程.
主要成果:
- 在与maleimidyl BoDIPY-FL反应时,工程Cp150-V124C VLPs自发交叉连接并形成转移稳定状态.
- 在减少剂的存在下,VLP分离,通过生物物理技术确认.
- 分离呈现出延迟阶段,与数学模型预测的核化依赖机制一致.
- 在转移到肝瘤细胞的VLP中观察到类似的触发解离.
结论:
- 开发了一种可通用的化学生物学策略,以创建对环境有反应的VLP.
- 这种方法可以从VLP中控制货物释放,提高它们作为治疗交付平台的潜力.
- 设计的HBV VLP系统可用于针对药物输送的应用程序.
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