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Pacific Blue Taxoids to Detect Cell Inhibitors

Pacific Blue, unique chemical derivatives invented by university researchers, could be used to detect inhibitors of cellular efflux transporters and other agents.

Existing substrates of efflux transporters such as P-glycoprotein (P-gp) lack sensitivity. KU’s novel pacific blue toxoids (PB-Gly-Taxol) are sensitive substrates of the efflux transporter and bind microtubules in living cells. 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 cancer cells, and was a highly sensitive substrate of the multidrug resistance transporter P-glycoprotein (P-gp). PB-Gly-Taxol can detect inhibitors of P-gp in a wide range of adherent cell lines such as HeLa and suspension cell lines such as Jurkat, Raji, and Ramos that express low levels of this efflux transporter.

Detection of inhibitors of P-glycoprotein (P-gp) in a wide range of cell lines. KU’s pacific blue toxoids (PB-Gly-Taxol) enables unique opportunities for discovery of novel modulators of P-gp using high-throughput flow cytometry methods. Additionally, as a cell-permeable fluorescent mimic of paclitaxel (Taxol), PB-Gly-Taxol can be used to study mechanisms of this anticancer drug and its binding to microtubules in living cells.

These probes can be efficiently detected by confocal microscopy, and compatible with flow cytometry. The photophysical and chemical properties of Pacific Blue (PB) allow it to be efficiently excited with violet diode lasers at 405 nm.

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University of Kansas

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