Cell surface engineering by a modified Staudinger reaction.
Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is presented. A ligation modeled after the Staudinger reaction forms an amide bond by coupling of an azide and a specifically engineered triarylphosphine. Both reactive partners are abiotic and chemically orthogonal to native cellular components. Azides installed within cell surface glycoconjugates by metabolism of a synthetic azidosugar were reacted with a biotinylated triarylphosphine to produce stable cell-surface adducts. The tremendous selectivity of the transformation should permit its execution within a cell's interior, offering new possibilities for probing intracellular interactions.
Saxon
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Departments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Bertozzi
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CR
D000107:Acetylation; D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D001710:Biotin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D019921:Biotinylation; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D006001:Glycoconjugates / Q000378:metabolism; D006367:HeLa Cells; D006595:Hexosamines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007659:Ketones / Q000378:metabolism; D010084:Oxidation-Reduction; D010720:Phosphines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000378:metabolism
C405952:4-(2-(2-(2-(biotinylamino)ethoxy)ethoxy)ethoxy)aminocarbonyl-2-diphenylphosphinobenzoic acid; D001386:Azides; D005456:Fluorescent Dyes; D006001:Glycoconjugates; D006595:Hexosamines; D007659:Ketones; C405953:N-azidoacetylmannosamine; D010720:Phosphines; D013438:Sulfhydryl Compounds; D001710:Biotin