Angewandte Chemie - International Edition
Angewandte Chemie - International Edition
5 years ago

Synthesis of a Fluorescent Analogue of Paclitaxel that Selectively Binds Microtubules and Sensitively Detects Efflux by P-Glycoprotein

Synthesis of a Fluorescent Analogue of Paclitaxel that Selectively Binds Microtubules and Sensitively Detects Efflux by P-Glycoprotein
Zhe Gao, Molly M. Lee, Blake R. Peterson
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 β-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). The fluorophore normally linked to the anticancer drug paclitaxel (Taxol) to investigate its biological activity significantly alters its properties. To construct more drug-like fluorescent probes suitable for confocal microscopy and flow cytometry, Taxol was linked to the drug-like fluorophore Pacific Blue (PB). PB-Gly-Taxol bound the target protein β-tubulin with high affinity and high specificity, and exhibited substantial cytotoxicity towards HeLa cells.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201703298

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.