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面向生物学的合成:利用进化的力量
Hilde van Hattum1, Herbert Waldmann
1Max Planck Institute of Molecular Physiology , Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Journal of the American Chemical Society
|July 31, 2014
概括
科学家可以通过使用以生物学为导向的合成来发现新的生物活性小分子. 这种方法利用自然产品及其进化关系来探索化学空间,用于化学生物学和药物发现.
科学领域:
- 化学生物学 化学生物学
- 药物发现 药物发现 药物发现
- 有机化学 有机化学
背景情况:
- 小分子调节器对于生物研究至关重要,但广的化学空间是合成无法访问的.
- 自然产品与蛋白质共同进化,为探索生物相关化学空间提供了理想的起点.
- 物质和合成时间的限制阻碍了对潜在干扰分子的全面探索.
研究的目的:
- 将"以生物学为导向的合成"作为发现新型生物活性小分子的战略.
- 为了利用进化原理,有效地探索化学多样性.
- 引导化学生物学和药物发现的化合物库的开发.
主要方法:
- 基于核心支架的已知自然产品的结构分类.
- 在"自然产品树"中等级地排列自然产品.
- 标注生物活性的自然产品树,并允许直观的导航.
主要成果:
- 开发自然产品的分类系统.
- 创建一个可航行的"自然产品树",用于生物活性探索.
- 证明以生物学为导向的合成作为产生生物活性化合物库的原则.
结论:
- 以生物学为导向的合成有效地利用进化关系来发现新的生物活性分子.
- 这种方法加速了用于化学生物学研究的化学工具的识别.
- 它通过专注于生物相关的支架,为药物发现提供了强有力的战略.
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