ENGINEERING CHEMICAL-REACTIVITY ON CELL-SURFACES THROUGH OLIGOSACCHARIDE BIOSYNTHESIS

Cell surface oligosaccharides can be engineered to display unusual fun ctional groups for the selective chemical remodeling of cell surfaces. An unnatural derivative of N-acetylmannosamine, which has a ketone gr oup, was converted to the corresponding sialic acid and incorporated i nto cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. The ketone group on the cell surfac e can then be covalently ligated under physiological conditions with m olecules carrying a complementary reactive functional group such as th e hydrazide. Cell surface reactions of this kind should prove useful i n the introduction of new recognition epitopes, such as peptides, olig osaccharides, or small organic molecules, onto cell surfaces and in th e subsequent modulation of cell-cell or cell-small molecule binding ev ents. The versatility of this technology was demonstrated by an exampl e of selective drug delivery. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate.