合成一种强效的葡萄芽蛋白:合理设计添加良性复杂性
Oliver Allemann1, Manuela Brutsch1, John C Lukesh1
1Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|June 30, 2016
概括
研究人员合成了一种具有良性复杂性 (ABC) 的新型vinblastine类似物,其生物活性增加了10倍. 这种合成方法克服了传统方法修改天然产品的局限性.
科学领域:
- 自然产品合成
- 医学化学
- 有机合成
背景情况:
- 维布拉斯等天然产品在医学上至关重要,
- 传统的合成和半合成方法难以有效地简化或衍生这些复杂的结构.
研究的目的:
- 开发一种具有增强生物活性的新型合成维布拉斯类似物.
- 通过晚期衍生或生物合成途径克服自然产品的修改局限性.
主要方法:
- 利用总合成的进展,制造出具有设计增加良性复杂性 (ABC) 的vinblastine模拟物.
- 采用一个修改后的,强大的前期单阶段vindoline-catharanthine合策略.
- 与天然产品合成相比,获得了更高的二元选择性.
主要成果:
- 合成维布拉斯类型的生物活性提高了10倍.
- 新的化合物包含了增加的分子复杂性,没有新的功能组,保留了自然特征.
- 通过半合成或生物合成修饰,无法获得这种类型的类似物.
结论:
- 总合成为复杂的天然产品提供了可行的途径,具有增强的治疗特性.
- 开发的合成策略提供了一种强有力的方法来获取新型温布拉斯衍生物.
- 设计的分子复杂性可以显著提高天然产品的功效.
相关概念视频
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...