A new way to engineer cells: The Staudinge...( BERKELEY CA -- No the Staudinger...)

BERKELEY, CA -- No, the "Staudinger ligation" isn't the latest Robert Ludlum thriller; it's a new chemical reaction in a growing arsenal of cell engineering techniques developed by Carolyn Bertozzi of the Department of Energy's Lawrence Berkeley National Laboratory, a pioneer in modifying the surfaces of living cells.

With her student Eliana Saxon, Bertozzi, a member of Berkeley Lab's Materials Sciences and Physical Biosciences Divisions and an associate professor of chemistry at the University of California at Berkeley, describes the Staudinger ligation in the March 17 issue of Science magazine.

Bertozzi and her colleagues have engineered human cells to display markers on oligosaccharides, the complex natural sugars that crowd cell surfaces. Through ligation with specific reagents, the markers provide new ways of labeling cells as targets for cancer therapy; adhering cells to nonbiological materials such as medical implants; forming new receptors for viral-mediated gene transfer; and other functions.

Unlike the ketone markers Bertozzi developed earlier, which may encounter interference from natural ketone metabolites inside the cell, the new Staudinger ligation yields azide markers that react exclusively with nonbiological groups. Since azides (a class of compounds with three nitrogen atoms) do not react with any other biological molecules outside or inside the cell, they hold promise for engineering the cell's interior as well as its surface.

"In all cellular engineering, the nature of the chemistry is key," Bertozzi says. "We need reactions that are stable in a watery environment at body temperature, that are highly selective, and that won't interfere with normal cell processes or with each other -- that are what we call 'orthogonal' to cellular components. That means we have to create new reactions."

Casting about for a reaction that was suitably orthogonal and harmless to cells, Bertozzi remembered "one of my favorite reacti
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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
15-Mar-2000