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UC San Diego and Genentech scientists develop potentially disruptive antibody sequencing technology
Date:12/19/2008

it2). Bandeira's co-authors on the Nature Biotechnology paper include UC San Diego computer science and engineering professor Pavel Pevzner, director of the Calit2-based Center for Algorithmic and Systems Biology (CASB); and three researchers from the Protein Chemistry Department of San Francisco-based Genentech: Victoria Pham, David Arnott, and Jennie R. Lill.

Shotgun protein sequencing will be particularly useful when complementary DNA (cDNA) or the original cell line is not available, or if there is a need to verify the integrity and effectiveness of an antibody after the cell has undergone changes subsequent to the original sequencing.

"Antibodies are indispensable in biomedical research and they are widely used as diagnostic and therapeutic agents," said Genentech's Jennie Lill. "DNA sequencing is routinely used in the initial characterization of monoclonal antibodies, but subsequent mutations and other changes mean that further protein level analysis is needed. So it is critical to sequence the antibodies for a variety of reasons, from monitoring the integrity of the molecule, to troubleshooting performance in pre-clinical assays."

Until now, the only viable option for sequencing an antibody has been a process known as Edman degradation, named for Swedish chemist Pehr Edman. (The technique was used in the sequencing of insulin, for which the Nobel Prize in Chemistry was awarded in 1958.) While Edman degradation remains a low-throughput and time-consuming approach, no fast substitute for this technique was found in the last half-century.

Bandeira and his colleagues proposed to substitute this ancient technique with protein sequencing based on mass spectrometry.

While mass spectrometry routinely is used to sequence short fragments of proteins (called peptides), no techniques for sequencing entire proteins were available until recently. The key bottleneck has been computing rather than experiment, since the challenge o
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Contact: Doug Ramsey
dramsey@ucsd.edu
858-822-5825
University of California - San Diego
Source:Eurekalert  

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