诺维奥辛通过刺激脂多糖转移来增强聚胺的活性
Michael D Mandler1, Vadim Baidin1, James Lee1
1Department of Chemistry and Chemical Biology , Harvard University , Cambridge , Massachusetts 02138 , United States.
Journal of the American Chemical Society
|May 11, 2018
概括
针对脂聚糖 (LPS) 传输增强分子的诺沃生物素衍生物
科学领域:
- 微生物学
- 药物发现
- 生物化学
背景情况:
- 格拉姆阴性细菌具有具有挑战性的外膜阻碍抗生素的有效性.
- 像胆固醇这样的多胺是最后的抗生素, 但具有毒性.
- 通过促进外膜透,诺维奥辛与聚米辛产生协同作用.
研究的目的:
- 合成和评估具有独特活动的新生素衍生物.
- 调查LptB刺激在多素-新生物素协同作用中的作用.
- 开发改善的组合疗法治疗格兰阴性感染.
主要方法:
- 新型诺波类药物的合成.
- 测试 DNA 陀螺酶抑制和 LptB 刺激的分离.
- 对多素的协同杀伤性进行评估.
主要成果:
- 一种刺激LptB但不抑制DNA旋转酶的新生物素模拟物增强了polymyxin的致命性.
- 这表明脂多糖体 (LPS) 运输激素对协同作用有显著的贡献.
- 其他具有增强的LptB结合的类型与多素的效果更强.
结论:
- 刺激LPS运输是新生物素-多胺协同作用的关键机制.
- 优化的诺波类药物可以提高多素的疗效和安全性.
- 针对LPS运输提供了一个有前途的策略来对抗阴性细菌.
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