曼诺胺,一种来自Streptomyces hygroscopicus的新型抗菌糖,LL-AC98
Haiyin He1, R Thomas Williamson, Bo Shen
1Department of Natural Products Chemistry, Chemical Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA. heh@wyeth.com
Journal of the American Chemical Society
|August 15, 2002
概括
新型曼诺胺 (1-5) 对MRSA和VRE等耐药细菌表现出强烈的活性. 它们独特的结构,包括一种不寻常的氨基酸和曼诺,是它们抗菌功效的关键.
科学领域:
- 微生物学 微生物学
- 药用化学 医学化学
- 有机化学 有机化学
背景情况:
- 耐甲素的葡萄球菌 (MRSA) 和耐万素的肠球菌 (VRE) 构成了严重的公共卫生威胁.
- 对抗这些耐药病原体的新型抗生素的开发是一个关键的未满足的医疗需求.
- 循环和它们的糖化衍生物代表了一类有前途的抗菌剂.
研究的目的:
- 发现和描述具有针对MRSA和VRE的活性的新型抗生素.
- 为了阐明这些新化合物的化学结构.
- 为了研究结构-活性关系,控制它们的抗菌功效.
主要方法:
- 从微生物来源净化新型抗生素化合物.
- 使用先进的光谱技术 (例如NMR,质谱学) 进行结构阐明.
- 化学修饰和转化研究以确认结构特征和评估活性.
主要成果:
- 五种新型抗生素的分离和表征,曼诺胺素α-epsilon (1-5).
- 鉴定了一种独特的结构特征:含有阿尔法-氨基-β- [4'-(2'-iminoimidazolidinyl) ]-β-hydroxypropionic 酸 (Aiha) 的两个立体异构体的糖基化循环六.
- 证明在末端曼诺斯部分上存在和放置异利基对抗MRSA和VRE的抗菌活性至关重要.
结论:
- 曼诺菌素代表了一种新的抗生素类别,具有针对具有挑战性的耐药细菌的显著潜力.
- 不寻常的氨基酸Aiha和特定的糖化模式是mannopeptimycins抗菌谱和功效的关键决定因素.
- 对曼诺胺的进一步研究可能会导致开发新的治疗药物来对抗抗生素耐药性.
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