Enzymes May Improve Delivery Of Anticancer Drug Derived From The Pacific Yew Tree

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ENZYMES MAY IMPROVE DELIVERY OF ANTICANCER DRUG DERIVED FROM THE PACIFIC YEW TREE

WASHINGTON -- Scientists today report making modifications to the promising anticancer drug paclitaxel, originally isolated from the Pacific yew tree, that they say may enable it to be more soluble in a patient's body and therefore more effective. The drug's limited solubility has complicated its efficacy in cancer treatment.

The study shows -- for the first time -- that enzymes can be used to boost the drug's water solubility, providing the anticancer agent with a better delivery system, according to Dr. Jonathan S. Dordick of the University of Iowa. The research was a collaboration between Dordick, Dr. Douglas S. Clark at the University of California, Berkeley, and scientists at EnzyMed, Inc. in Iowa City, Iowa. Their work is reported in the November 26 issue of the Journal of the American Chemical Society, published by the world's largest scientific society.

While other researchers have made water-soluble derivatives of paclitaxel using more traditional chemical methods, this three-way team is the first to use biocatalysis. Because paclitaxel is a complicated molecule, it is often difficult to control what part of the molecule will be changed in a chemical reaction. But Dordick, Clark and EnzyMed used commercially available enzymes to maintain control of and catalyze a reaction that transforms paclitaxel into a potential prodrug with unusually high water solubility. "The expectation," Dordick contends, "is that once it is in the body, the modifications made to paclitaxel to increase its solubility come off, leaving the potent paclitaxel to do its job."

The research team's new and relatively simple method has dramatically increased paclitaxel's solubility 1700-fold, among the highest on record so far.

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11/25/97