The researchers discovered that the metabolic pathways for cell-surface oligosaccharide biosynthesis are permissive for unnatural substrates. They synthesized an unnatural sugar bearing a reactive functional group, the ketone, and fed this substrate to a variety of cell types. Metabolic uptake and incorporation into cell surface oligosaccharides resulted in the expression of ketone groups on the cell surface. The ketone is chemically unique to the cell surface, in that none of the naturally occurring amino acids, sugars or lipids possess a ketone, and it serves as a molecular handle for remodeling cells in a chemically defined fashion. The researchers demonstrated the versatility of this technology in a new approach to selective drug delivery. Ketone groups were incorporated into sialic acid, a sugar that is prevalent on cancer cells, and then ligated with hydrazide-conjugated protein toxins resulting in selective cell death.

In addition to biomedical applications, chemical cell surface remodeling can be utilized in the directed adhesion of living cells to hydrazide-coated materials and the patterning of cells on defined surfaces. Since the expression of reactive functional groups is achieved solely through metabolic processes, this strategy is amenable to in vivo applications such as artificial tissue construction and diagnostic imaging.

Lara K. Mahal, Kevin J. Yarema, Carolyn R. Bertozzi, "Engineering Chemical Reactivity on Cell Surfaces Through Oligosaccharide Biosynthesis,"Science, 276, 1125 (1997).