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Protein engineered to detect nerve gas

DURHAM, N.C. -- Duke University Medical Center biochemists have used computational design to engineer and construct a protein that could sense the nerve agent soman. They said their achievement constitutes a proof-of principle that such engineered proteins can be made to detect nerve agents such as sarin and other toxic substances.

Such proteins could be incorporated into detectors, which might resemble smoke detectors and could be widely deployed as early-warning alarms, weapons monitors or in the decontamination process after an attack. The detector could not only warn of the presence of the nerve agent, but act as a continuous monitor of its levels.

Led by Associate Professor of Biochemistry Homme Hellinga, Ph.D., the researchers reported their achievement in a paper published online May 17, 2004 in the Proceedings of the National Academy of Sciences. Besides Hellinga, other co-authors of the PNAS paper were Malin Allert, Shahir Rizk and Loren Looger. Their research is sponsored by the Defense Advanced Research Projects Agency.

In the PNAS paper, Helling and his colleagues described how they had designed a protein that detects a surrogate for soman, called pinacolyl methyl phosphonic acid (PMPA), which has the same basic chemical structure as soman, but is less toxic. Soman is a nerve agent first invented by the Germans before World War II and manufactured in large quantities by the former Soviet Union.

In developing the PMPA detector, the Duke researchers used the same general design technique that they had previously used to tailor proteins to sense glucose, lactate, TNT and the brain chemical serotonin.

They began with proteins, called "periplasmic binding proteins," from the gut bacterium E. coli. These proteins are normally part of the bacterium's chemical-sensing system by which it detects nutrients. Such protein receptors detect their target molecule via an "active site" that has a precise complementary shape and bin
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Contact: Dennis Meredith
dennis.meredith@duke.edu
919-681-8054
Duke University Medical Center
3-Jun-2004


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