5'-O-hex-5-ynoylshowdomycin | 1228282-89-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5'-O-hex-5-ynoylshowdomycin
• CAS: 1228282-89-0
• 化学式: C₁₅H₁₇NO₇
• 分子量: 323.302
• InChiKey: AFDTYZGNCHYDBA-JXJLXUTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.59
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  122.16
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  Showdomycin 、 5-己炔酸 在 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.17h， 生成 5'-O-hex-5-ynoylshowdomycin 、 5'-O-hex-5-ynoyl-1'-epi-showdomycin
  参考文献：
  名称：

  Showdomycin as a Versatile Chemical Tool for the Detection of Pathogenesis-Associated Enzymes in Bacteria

  摘要：

  Showdomycin is a potent nucleoside antibiotic that displays a high structural similarity to uridine and pseudouridine. No detailed target analysis of this very unusual electrophilic natural product has been carried out so far. To unravel its biological function, we synthesized a showdomycin probe that can be appended with a fluorophor or a biotin marker via click chemistry and identified diverse enzymes which were important for either the viability or virulence of pathogenic bacteria. Our results indicate that the antibiotic effect of showdomycin against Staphylococcus aureus may be due to the inhibition of various essential enzymes, especially MurA1 and MurA2, which are required for cell wall biosynthesis. Although real-time polymerase chain reaction revealed that the MurA2 gene was expressed equally in four S. aureus strains, our probe studies showed that MurA2 was activated in only one multiresistant S. aureus strain, and only this strain was resistant to elevated concentrations of the MurA inhibitor fosfomycin, suggesting its potential role as an antibiotic bypass mechanism in the case of MurA1 inhibition. Moreover, we utilized this tool to compare enzyme profiles of different pathogenic strains, which provided unique insights in regulatory differences as well as strain-specific signatures.

  DOI：

  10.1021/ja909150y