像哨兵一样的单分子葡萄糖结合物向树突细胞莱克,释放一种抗HIV药物
Qiang Zhang1, Lu Su, Jennifer Collins
1Department of Chemistry, University of Warwick , CV4 7AL Coventry, United Kingdom.
Journal of the American Chemical Society
|February 27, 2014
概括
在纳米分子度下,新型的环氧德克斯糖结合物抑制了HIV与DC-SIGN的结合. 这些化合物还显示出针对抗癌和抗HIV药物的向药物递送的潜力.
科学领域:
- 碳水化合物化学 碳水化合物化学
- 聚合物化学 聚合物化学
- 生物结合化学 生物结合化学
背景情况:
- 人类的跨膜讲蛋白DC-SIGN在HIV感染的初始阶段发挥着至关重要的作用,通过与病毒包膜蛋白gp120结合.
- 开发有效的DC-SIGN/gp120相互作用抑制剂是预防和治疗艾滋病毒的关键策略.
- 基于循环德的糖结合物为设计具有潜在生物应用的多价值碳水化合物结构提供了多功能平台.
研究的目的:
- 合成新型基于循环德的葡萄糖结合物,包括葡萄糖集群和恒星葡萄糖聚合物.
- 为了评估这些糖结合物的结合亲和力与人体莱克DC-SIGN.
- 评估它们作为DC-SIGN/HIV gp120相互作用的抑制剂和药物输送载体的潜力.
主要方法:
- 使用CuAAC Huisgen合和铜介导活基聚合物的组合合成基于循环德的糖合物.
- 亲和结合测试用于量化糖酸和DC-SIGN之间的相互作用.
- 抑制试验测量了葡萄糖合物对HIV gp120结合DC-SIGN的阻断作用.
- 使用星块甘聚合物的水抗癌和抗艾滋病毒药物的药物加载和释放研究.
主要成果:
- 合成的葡萄糖结合物,包括葡萄糖集群和恒星葡萄糖聚合物,证明了高亲和度与DC-SIGN结合.
- 这些化合物有效地抑制了HIV包膜蛋白gp120在纳米分子度下与DC-SIGN的结合.
- 星级区块甘油聚合物表现出对疏水性抗癌和抗艾滋病毒药物的高负载能力.
结论:
- 基于环德的糖结合物是DC-SIGN/HIV gp120相互作用的强有力的抑制剂.
- 开发的明星块甘油聚合物显示出对先进的HIV治疗方法和智能药物输送系统的重大前景.
- 这项研究为开发基于碳水化合物的抗病毒剂和药物输送平台开辟了新的途径.
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