一个直角功能性红色素类似物的前体指导生物合成:在核糖体宏化物结合口袋中的选择性
Colin J B Harvey1, Joseph D Puglisi, Vijay S Pande
1Department of Chemistry, Stanford University, Stanford, California 94305, USA.
Journal of the American Chemical Society
|June 30, 2012
概括
研究人员发现了新的基和基替代的宏化物,其抗菌活性与红红A相当. 他们还开发了15-propargyl erythromycin A,一种具有增强化学修饰能力的新型抗生素.
科学领域:
- 药用化学 医学化学
- 微生物学 微生物学
- 合成生物学 合成生物学
背景情况:
- 宏类抗生素,如红红素A,对于治疗细菌感染至关重要.
- 开发具有改进性质的新型类似物对于打击抗生素耐药性至关重要.
研究的目的:
- 为了确定具有强烈抗菌活性的新型宏类相应物.
- 探索前体修饰的结构-活性关系.
- 开发具有增强化学功能的新型红红素A衍生物.
主要方法:
- 利用化学遗传策略进行前体指导生物合成.
- 采用殖民地生物测试来选6 - 脱氧氨酸D类似物.
- 合成和表征了新的基尼尔,基尼尔和基替代的宏化物.
主要成果:
- 鉴定出一种新的类别的基和基替代的宏类,其活性与红色素A相似.
- 发现抗生素活性对前体大小和不和的显著依赖.
- 成功合成了15-propargyl红色素A,一种具有正交函数组的强效抗生素.
结论:
- 前体修饰是一种可行的策略,用于产生新型宏类抗生素.
- 15-propargyl erythromycin A代表了一个有前途的新型抗生素支架,用于进一步开发和化学修改.
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