期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 56, 期 24, 页码 6927-6931出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201703298
关键词
antitumor agents; confocal microscopy; drug design; fluorescent probes; paclitaxel
资金
- NIH [P20-GM103638, P20-GM103418, R01-CA211720]
- G. Harold and Leila Y. Mathers Charitable Foundation
- NIH Dynamic Aspects of Chemical Biology Training Grant at the University of Kansas [T32-GM08545]
The anticancer drug paclitaxel (Taxol) exhibits paradoxical and poorly understood effects against slow-growing tumors. To investigate its biological activity, fluorophores such as Oregon Green have been linked to this drug. However, this modification increases its polarity by approximately 1000-fold and reduces the toxicity of Taxol towards cancer cell lines by over 200-fold. To construct more drug-like fluorescent probes suitable for imaging by confocal microscopy and analysis by flow cytometry, we synthesized derivatives of Taxol linked to the drug-like fluorophore Pacific Blue (PB). We found that PB-Gly-Taxol bound the target protein beta-tubulin with both high affinity in vitro and high specificity in living cells, exhibited substantial cytotoxicity towards HeLa cells, and was a highly sensitive substrate of the multidrug resistance transporter P-glycoprotein (P-gp).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据