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Tailor-made recombinant proteins in mammals
Date:2/9/2009

BERKELEY, CA A new way to direct chemical modifications to specific sites on recombinant proteins including the monoclonal antibodies so important in the pharmaceutical industry has been developed by Carolyn Bertozzi and her colleagues at the U.S. Department of Energy's Lawrence Berkeley National Laboratory and the University of California at Berkeley.

Many therapeutic proteins, including insulin for diabetes, can be made in bacterial systems like Escherichia coli, but most protein pharmaceuticals must be expressed in cultured mammalian cells. The researchers have now found a way to extend the use of "aldehyde tags," which they previous developed for recombinant proteins expressed in bacteria, to label proteins that can only be expressed by mammalian systems.

"Proteins made with recombinant DNA are a major weapon in the armory against disease," says Bertozzi, who is a member of Berkeley Lab's Materials Sciences and Physical Biosciences Divisions and director of the Molecular Foundry, a Department of Energy (DOE) nanoscience user research facility. "But protein therapeutics are far from perfect. Many have short half-lives, so the patient must inject them repeatedly. And it is often difficult to introduce novel features into a recombinant protein."

While a specific chemical change can extend a protein's lifetime or turn it into a target for diagnostic imaging, for example, or convert an antibody into a drug that seeks out and attacks cancer cells, directing a chemical modification to the right place in the protein can be a challenge.

"Some protein modification methods have been around for a long time; typically they make use of the amino acid residue lysine. But there are lots of kinds of proteins in a cell, and any of them may include dozens or even hundreds of lysines, so it's hard to modify just one and not all of them," says Bertozzi, who is also a professor in the Departments of Chemistry and Molecular and Cell
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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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