Novel polymer could improve protein-b...( DURHAM N.C. A new method for attach...)

DURHAM, N.C. A new method for attaching a large protective polymer molecule to a protein appears to improve protein drugs significantly.

Bioengineers at Duke University developed the new approach and demonstrated in an animal model that the newly created protein-polymer combinations, known as conjugates, remained in circulation significantly longer than an unprotected protein.

The scientists say they are encouraged that their findings represent a new strategy to improve the efficacy of protein drugs.

Protein-based drugs are an increasingly important new class of drugs, said Ashutosh Chilkoti, Theo Pilkington Professor of Biomedical Engineering at Duke's Pratt School of Engineering. He cited such examples as insulin for the treatment of diabetes and more exotic "magic bullet" antibodies like herceptin that are used to treat certain cancers.

Unmodified proteins that are injected into the blood are quickly recognized by the body and broken down or cleared by the body's defense system, which limits their effectiveness as drugs. To get around this problem, drug makers have been attaching another molecule, a polymer known as polyethyleneglycol (PEG), to the protein in order to protect it. But this approach has its own drawbacks.

"The current method of combining the two molecules often only works with 10 to 20 percent efficiency, so that a lot of the very expensive starting materials are wasted," said Chilkoti, who had the results of his team's experiments published this week online in the Proceedings of the National Academy of Sciences. "Additionally, the two large molecules are attached by a small chemical link and often these linkages can occur at many different sites on the protein, so the final product is poorly defined."

Chilkoti took a different approach. Instead of combining two large molecules, he grew the polymer out from the protein itself, increasing the efficiency of the protein by more than 70
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