两种天然化合物作为潜在的抑制剂对抗Helicobacter pylori和Acinetobacter baumannii的IspD酶
Xiaoyu Chen1, Huilin Zhao2, Chuandong Wang1
1Helmholtz International Lab, State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.
研究人员确定了天然化合物 - - 罗斯马林酸和坦辛二甲硫酸盐 - - 抑制甲基利酸 (MEP) 路径酶. 这些发现为开发针对重要细菌通路的抗菌剂提供了新的途径.
科学领域:
- 生物化学 生物化学
- 微生物学 微生物学
- 药物发现 药物发现 药物发现
背景情况:
- 甲基酸 (MEP) 途径对于细菌,原生动物和植物中的异类合成至关重要,与人类酸 (MVA) 途径不同.
- 异oprenoids对于许多生理过程至关重要,使MEP通路酶成为抗菌药物开发的有吸引力的目标.
研究的目的:
- 为了描述Helicobacter pylori IspDF和Acinetobacter baumannii IspD.的酶活性和蛋白质结构.
- 使用已批准的药物库,选抑制MEP通路酶的化合物,特别是IspD和IspDF.
主要方法:
- 对HpIspDF和AbIspD的酶活性和蛋白质结构的表征.
- 基于直接相互作用的热转移试验用于针对AbIspD的化合物选.
- 在体外抑制试验和对H. pylori的抗菌检测.
主要成果:
- 从经批准的药物库中确定了27种可能与AbIspD结合的命中化合物.
- 罗斯马林酸和坦辛二甲硫酸盐通过与基质MEP竞争来抑制HpIspDF和AbIspD.
- 坦辛二甲硫酸盐显示对H.pylori有抗菌作用.
结论:
- 两种天然产品 - - 罗斯马林酸和坦辛二甲硫酸盐 - - 被确定为IspD抑制剂.
- 这些化合物代表了开发针对细菌MEP途径的新型抗生素的有希望的线索.
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