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Novel polymer could improve protein-based drugs
Date:8/19/2009

percent and greatly extending the amount of time it remained active in a living model.

"We also addressed the problem of getting a pure and well-defined product by growing the polymer from a single, unique site on the protein," he said. "Another twist to our work is that instead of using PEG, we used a somewhat different polymer that turns out to be as good and perhaps even better than PEG in extending circulation of the protein in the body."

There are many protein-polymer based medications in use today, such as human growth hormones, drugs to stimulate blood cell formation in cancer patients and anti-viral agents. Chilkoti will be reviewing existing protein-polymer drugs to determine if the new technique can improve their effectiveness.

In their experiments, the researchers used myoglobin, a protein responsible for creating the red pigments that give meat its color. Instead of creating a chemical bond between myoglobin and the polymer, the Duke researchers chose a specific spot on the protein, known as the N-terminus, and then grew the polymer from that specific location. Every protein has an N-terminus, so this method should be broadly useful, Chilkoti said.

After demonstrating they could create a stable compound using the new method, the researchers tested how well it worked by comparing its actions to the conventional compound in mice.

"The conventional compound myoglobin had a half-life of three minutes and was totally eliminated by two hours," Chilkoti explained. "By contrast, the new compound had a half-life 40 times greater and remained in circulation for 18 hours. The longer a protein remains in the system and is active, the more it helps the patient."

"The dramatic improvement in how the new compound acted encourages us that this new approach will have broad applications in improving the efficacy of many protein drugs," Chilkoti said.

Another benefit of this approach, according to Chilkoti,
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Contact: Richard Merritt
Richard.merritt@duke.edu
919-660-8414
Duke University
Source:Eurekalert

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