title: Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis.
abstract: Cell surface oligosaccharides can be engineered to display unusual functional groups for the selective chemical remodeling of cell surfaces. An unnatural derivative of N-acetyl-mannosamine, which has a ketone group, was converted to the corresponding sialic acid and incorporated into cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. The ketone group on the cell surface can then be covalently ligated under physiological conditions with molecules carrying a complementary reactive functional group such as the hydrazide. Cell surface reactions of this kind should prove useful in the introduction of new recognition epitopes, such as peptides, oligosaccharides, or small organic molecules, onto cell surfaces and in the subsequent modulation of cell-cell or cell-small molecule binding events. The versatility of this technology was demonstrated by an example 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.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Mahal
authors.forename: K J
authors.initials: KJ
authors.lastname: Yarema
authors.forename: C R
authors.initials: CR
authors.lastname: Bertozzi
mesh_terms: D001360:Avidin / Q000494:pharmacology / Q000633:toxicity; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D005434:Flow Cytometry; D006001:Glycoconjugates / Q000378:metabolism; D018922:HL-60 Cells; D006367:HeLa Cells; D006595:Hexosamines / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D007659:Ketones / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D009844:Oligosaccharides / Q000096:biosynthesis*; D012276:Ricin / Q000378:metabolism / Q000633:toxicity; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D006001:Glycoconjugates; D006595:Hexosamines; D007659:Ketones; C105871:N-levulinoyl mannosamine; D009844:Oligosaccharides; D014415:Tunicamycin; D001360:Avidin; C053311:biotin hydrazide; D001710:Biotin; D012276:Ricin; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; C002022:N-acetylmannosamine