结构的muraymycins,新的糖生物合成抑制剂的结构
Leonard A McDonald1, Laurel R Barbieri, Guy T Carter
1Wyeth-Research, 401 North Middletown Road, Pearl River, New York 10965, USA. mcdonal@wyeth.com
Journal of the American Chemical Society
|August 29, 2002
概括
研究人员发现了muraymycins,这是一种新型核酸-脂抗生素家族,通过抑制类甘油生物合成,对各种细菌有效. 穆雷米辛A1在小鼠中显示出对黄金葡萄球菌感染的显著保护.
科学领域:
- 微生物学 微生物学
- 药用化学 医学化学
- 自然产品 化学 化学
背景情况:
- 核酸-脂抗生素对于对抗细菌感染至关重要.
- Streptomyces 种类是众所周知的多种生物活性化合物的来源.
- 抗生素耐药性的出现需要发现新的抗菌剂.
研究的目的:
- 从Streptomyces sp.中分离和描述新型抗生素. LL-AA896. 这是一个很大的问题.
- 为了阐明新发现的化合物的化学结构.
- 评估新型抗生素家族的抗菌活性和作用机制.
主要方法:
- 使用各种染色学技术净化抗生素.
- 通过NMR光谱学,质谱学和降解研究进行结构阐明.
- 在实验室对临床分离物进行抗微生物敏感性测试和体内疗效研究.
主要成果:
- 19个muraymycin化合物的隔离和结构确定,这是一个新的抗生素家族.
- 穆雷米辛在体外表现出广泛的抗菌活性 (MIC 2至>64μg/mL).
- 抑制糖糖生物合成被确定为作用机制;Muraymycin A1在体内证明了对黄金葡萄球菌的有效性.
结论:
- 穆雷米辛代表了一类具有显著抗菌潜力的新型核酸-脂抗生素.
- 结构特征,包括脂肪酸替代物和氨基糖,对生物活性至关重要.
- 穆拉米辛是作为抗菌剂进一步开发的有希望的候选者.
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