关于聚化二乙烯及其衍生物对甲状腺激素的生物分子竞争机制的研究
Shaoheng Liu1, Rong Hu2, Hao Zhan3
1Engineering Research Center of Hunan Province for Recycling Technology of Electroplating Wastewater, Hunan Provincial Key Laboratory of Water Treatment Functional Materials, College of Chemistry and Material Engineering, Hunan University of Arts and Science, Changde 415000, China.
Molecules (Basel, Switzerland)
|November 14, 2023
概括
聚二乙烯 (PBDE) 和其衍生物通过竞争性地与运输蛋白结合来破坏甲状腺激素. 较高的化和化增加了这种干扰,影响了甲状腺功能.
科学领域:
- 环境化学环境化学
- 毒理学 毒理学 毒理学
- 内分泌学 在内分泌学.
背景情况:
- 聚二乙烯 (PBDE) 是常见的阻燃剂,具有已知的内分泌干扰潜力.
- PBDE及其氧化衍生物 (OH-PBDE) 干扰激素系统,特别是甲状腺激素.
- 甲状腺激素转化素 (TTR) 是一种关键蛋白质,负责甲状腺激素的运输.
研究的目的:
- 量化评估PBDE和OH-PBDE对TTR的结合能力.
- 评估PBDE,OH-PBDE和甲状腺激素之间对TTR结合的竞争性相互作用.
- 阐明PBDE和OH-PBDE对甲状腺系统的干扰机制.
主要方法:
- 为TTR结合准备一个特定的光探针 (FITC-T4,F-T4).
- 使用光谱学和火原理量化测量结合能力.
- 分析PBDE (BDE-209,BDE-47) 和OH-PBDE (6-OH-BDE-47) 与F-T4.4之间的竞争相互作用.
- 使用AutoDock进行分子对接模拟,以分析OH-PBDE干扰T4.
主要成果:
- 在不同的PBDE和OH-PBDE中观察到不同程度的TTR结合干扰.
- 化和化水平的增加与对TTR的更强的竞争性结合有关.
- 高度的PBDE/OH-PBDE增强了竞争中的替代性,直到一定值.
- 具有4个原子和与T4具有结构相似性的OH-PBDE显示出比T4本身更强的TTR结合亲和力.
结论:
- PBDE和OH-PBDE通过与TTR结合来干扰甲状腺激素的运输.
- 化,化和度的程度显著影响破坏性潜力.
- 与甲状腺素 (T4) 的结构相似性增强了OH-PBDE与TTR的结合亲和力,对甲状腺激素稳定有显著的风险.
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