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细胞吸收氨基糖化物,瓜尼丁糖化物和聚氨酸
Nathan W Luedtke1, Peter Carmichael, Yitzhak Tor
1Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, USA.
Journal of the American Chemical Society
|October 9, 2003
概括
像尼奥米B和托布拉米这样的氨基糖类药物具有较差的细胞吸收. 将它们的氨基转化为瓜尼丁组显著增强了细胞吸收,改善了药物递送潜力.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 药物运输 药物运输 药物运输
背景情况:
- 氨基糖化物 (例如,neomycin B,tobramycin) 在真核细胞中显示出有限的细胞吸收.
- 通过将氨基组转化为瓜尼丁部分的氨基基化物的化学修饰可以增强细胞透.
研究的目的:
- 为了合成和评估BODIPY标记的氨基甘油酸和瓜尼丁甘油酸的细胞吸收.
- 为了比较这些改性化合物的膜转位和细胞内定位.
主要方法:
- 合成BODIPY结合的氨基糖化物和瓜尼丁糖化物.
- 使用光激活细胞分类 (FACS) 进行定量吸收分析.
- 使用光显微镜进行细胞局部化和膜转位的定性评估.
主要成果:
- 图布拉米和尼奥米B的关氨基化导致细胞吸收分别增加了10倍和20倍.
- 与光聚氨酸酸相比,瓜尼迪诺-氨酸B的细胞吸收率更高.
- 瓜尼迪诺-尼奥米辛B抑制了聚氨酸的吸收,这表明一个共享的细胞吸收机制.
结论:
- 关氨基化是一种可行的策略,可以显著增强氨基糖的细胞吸收.
- 瓜尼尼丁糖化物可能利用类似的细胞吸收途径作为富含阿尔金宁的细胞透.
- 这些发现对开发改进的基于阿米诺糖的治疗药物具有增强的传递特性有影响.
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