碳水化合物-乳氨酸识别序列定义的异质多价格甘油聚合物
Daniela Ponader1, Pauline Maffre, Jonas Aretz
1Max Planck Institute of Colloids and Interfaces, Research Campus Golm , Am Mühlenberg 1, 14424 Potsdam, Germany.
Journal of the American Chemical Society
|January 15, 2014
概括
设计具有多种糖类型 (异种多重性) 的人工糖联体显著增强了与莱克受体的结合亲和力,为分子相互作用和药物开发提供了新的见解.
科学领域:
- 碳水化合物的化学成分
- 葡萄糖生物学 葡萄糖生物学
- 超分子化学 超分子化学
背景情况:
- 大自然利用多价值性来进行连接体-受体相互作用.
- 人工甘油聚合物模仿自然的多价值系统.
- 现有的糖仿制药往往缺乏有目的的异质性.
研究的目的:
- 为了合成序列定义的异种多价格的葡萄糖聚合物.
- 为了研究连接物异质性对结合亲和力的影响.
- 了解多价值结合的基本机制.
主要方法:
- 在控制合成的固体支上进行序列点击化学.
- 功能性构建块的逐步组装.
- 用曼诺,银河糖和葡萄糖合成异构多元的寡合物.
- 使用康卡纳瓦林A莱克受体进行亲和度测量.
- 使用STD-NMR和2fFCS. 的联结体/受体相互作用研究.
主要成果:
- 异种多元的甘油聚合物表现出比同种多元的类似物更高的亲缘关系.
- galaktose 残留物,虽然不结合,但通过硬质屏蔽增强了亲和力.
- 非结合性配体抑制了受体聚类.
- 绑定机制改变了特定的异构多元结构.
结论:
- 异种多元性对于设计强效的甘油聚合物至关重要.
- 控制的异质性为多价值结合提供了更深入的见解.
- 这种方法可以精确控制糖合物的结构和功能.
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