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The first engineering of cell surfaces in living animals

BERKELEY, CA -- Four years ago Carolyn Bertozzi, a member of the Materials Sciences Division at the Department of Energy's Lawrence Berkeley National Laboratory and a professor of chemistry at the University of California at Berkeley, introduced a new way of engineering the surfaces of cells, by arming cell-surface sugars to take part in a modified chemical reaction known as the Staudinger ligation.

The technique allows a variety of markers to be attached to cultured cells without disturbing their biological environment; it has proved valuable in fundamental studies of cell interactions and in the development of new techniques for interfacing cells with synthetic materials and devices.

Now Bertozzi and her colleagues have demonstrated the Staudinger ligation in remodeled cells of living mice. The ability to tag cell surfaces in living beings may someday allow the targeting of specific kinds of cells for noninvasive imaging, for developmental studies, and for treatment of disease.

"There was no precedent for what we were trying to do, which was to modify the cells of a living animal so that they could undergo a chemical reaction without physiological harm," says Bertozzi. "It was a particular challenge because the living animal is such a complex reaction vessel." The researchers report their results in the 19 August 2004 issue of Nature.

Key to their success is what Bertozzi calls the bio-orthogonality of the reaction, literally "at right angles" to biology: chemical reactions artificially induced on the cell surface must be highly selective and able to take place in the warm, watery physiological environment, but at the same time they must have no harmful biological effects.

The Staudinger ligation meets these requirements. It is a reaction between a functional group called an azide (a class of compounds with three nitrogen atoms) and a phosphine (a molecule containing a phosphorus atom). Neither azides nor phosphines h
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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
18-Aug-2004


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