自然产品结构的化学演变
Michael Grigalunas1, Susanne Brakmann2, Herbert Waldmann1,2
1Max-Planck-Institute of Molecular Physiology, Otto-Hahn Strasse 11, 44227, Dortmund, Germany.
Journal of the American Chemical Society
|February 21, 2022
概括
伪天然产品模仿大自然的化学结构, 这种方法将天然产品的碎片结合起来,制造出未在自然界中发现的新型生物相关化合物,扩大了新药的化学空间.
科学领域:
- 医学化学
- 化学生物学
- 药物发现
背景情况:
- 自然产品是通过进化过程发现的生物活性分子的重要来源.
- 探索新型化合物对于扩大生物相关化学空间至关重要.
- 现有的药物发现方法可能受自然产品的化学多样性限制.
研究的目的:
- 引入和定义伪天然产品的概念,用于药物发现.
- 概述设计和开发伪天然产品的工作流程.
- 证明伪天然产品在化学和生物研究中的普遍性和潜力.
主要方法:
- 使用自然产品结构的碎片式化合物开发.
- 自然产品碎片的新设计和组合.
- 生物活性合成化合物的化学信息分析.
- 伪自然产品与自然进化过程的比较.
主要成果:
- 伪天然产品保留了天然产品的生物相关性.
- 这些新型基架不是通过已知的生物合成途径产生的,导致新的化学类型.
- 其中很大一部分生物活性合成化合物被认为是伪天然产品.
- 伪天然产品代表了自然产品结构的由人类驱动的化学进化.
结论:
- 伪天然产品概念为发现新的生物活性化学物质提供了有效的策略.
- 这种方法扩大了可访问的化学空间,超出了自然存在的化合物.
- 伪天然产品是化学发现中自然进化的有价值的人造模拟物.
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