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板胺素的隔离,结构和绝对立体化学,是一种广泛的抗生素,使用反感差异敏感度策略发现
Sheo B Singh1, Hiranthi Jayasuriya, John G Ondeyka
1Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. sheo_singh@merck.com
Journal of the American Chemical Society
|September 7, 2006
概括
普拉西是一种新型抗生素,通过向FabF酶来抑制细菌脂肪酸合成. 这一发现为开发抗菌剂对抗阳性细菌提供了新的策略.
科学领域:
- 微生物学 微生物学
- 药用化学 医学化学
- 生物化学 生物化学
背景情况:
- 脂肪酸对于细菌的生存至关重要.
- 抑制脂肪酸合成是新抗菌药物的有希望的目标.
- 普拉坦西米辛是一种来自Streptomyces platensis的新型抗生素,具有针对格拉姆阳性细菌的广谱活性.
研究的目的:
- 发现和描述针对细菌脂肪酸合成的新型抗菌剂.
- 为了研究白金胺的作用机制.
- 阐明平坦西米及其衍生物的结构和生物活性.
主要方法:
- 基于目标的全细胞查使用反感觉差异灵敏度测试.
- 通过捕获和逆相HPLC进行隔离.
- 使用二维NMR和X射线晶体学阐明结构.
- 衍生和生物活性评估的6,7-dihydroplatensimycin.
主要成果:
- 在脂肪酸合成途径中,平坦西米辛选择性地抑制了凝结酶FabF.
- 环素环形状,而不是子反应性,是强酶结合的关键.
- 详细介绍了6,7-二平西米的分离,结构和活性.
结论:
- 普拉西米辛代表了一种针对细菌脂肪酸合成的新型抗生素.
- 柏金素对FabF的特异性抑制为抗菌药物开发提供了宝贵的头.
- 结构性见解,特别是环色环的作用,指导未来的衍生努力.
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