环境污染物和肺癌中的蛋白质不稳定:用于结构稳定的抗癌药物策略
Reza Rasoolzadeh1, Homa Faraji2,3, Leonardo Baptista4
1Department of Inorganic Chemistry, Institute of Chemistry, Fluminense Federal University, Niterói, Rio de Janeiro 24020-141, Brazil.
ACS omega
|January 26, 2026
概括
像氨基抗皮林 (AAP) 这样的环境污染物会破坏肺癌生物标志物的稳定性,这些生物标志物是益胃素释放 (Pro-GRP) 和超氧化物失突酶 (SOD). 抗癌药物Paclitaxel和Sotorasib显示出稳定这些蛋白质对污染物影响的潜力.
科学领域:
- 计算生物物理学的计算生物物理.
- 环境毒理学环境毒理学
- 分子药理学分子药理学
背景情况:
- 环境污染物双A (BPA) 和氨基抗皮林 (AAP) 与肺癌进展有关.
- 这些污染物可以改变蛋白质结构,可能会影响抗癌药物的疗效.
- 促胃素释放 (Pro-GRP) 和超氧化失突酶 (SOD) 是受污染物影响的关键肺癌生物标志物.
研究的目的:
- 研究BPA和AAP在Pro-GRP和SOD结构动态上的分子机制.
- 评估帕克利塔克塞尔和索托拉西布对污染物诱导的蛋白质不稳定性的稳定作用.
- 探索环境污染物,抗癌药物和肺癌中的蛋白质标之间的相互作用.
主要方法:
- 分子动力学 (MD) 模拟
- 分子对接是分子对接.
- 有约束力的免费能源计算 (MM/PBSA)
- 根平均平方偏差 (RMSD) 和根平均平方波动 (RMSF) 分析.
主要成果:
- 氨基抗皮林 (AAP) 显著破坏了Pro-GRP和SOD结构的稳定.
- 与AAP相比,双A (BPA) 显示出较轻的破坏稳定的作用.
- 帕克利塔克塞尔和索托拉西布通过减少波动和保持原生形状来证明蛋白质稳定.
- 发现抗癌剂可以调节关键残留物中的污染物结合,可能减轻不稳定.
结论:
- 环境污染物可以破坏关键肺癌生物标志物的结构和功能.
- 抗癌药物Paclitaxel和Sotorasib可能会抵消污染物诱导的蛋白质不稳定.
- 计算发现突出了环境暴露对肺癌治疗中药物蛋白相互作用的潜在影响.
- 需要实验验证,以确认这些计算预测的生物学和临床相关性.
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