title: Investigating cellular metabolism of synthetic azidosugars with the Staudinger ligation.
abstract: The structure of sialic acid on living cells can be modulated by metabolism of unnatural biosynthetic precursors. Here we investigate the conversion of a panel of azide-functionalized mannosamine and glucosamine derivatives into cell-surface sialosides. A key tool in this study is the Staudinger ligation, a highly selective reaction between modified triarylphosphines and azides that produces an amide-linked product. A preliminary study of the mechanism of this reaction, and refined conditions for its in vivo execution, are reported. The reaction provided a means to label the glycoconjugate-bound azidosugars with biochemical probes. Finally, we demonstrate that the cell-surface Staudinger ligation is compatible with hydrazone formation from metabolically introduced ketones. These two strategies provide a means to selectively modify cell-surface glycans with exogenous probes.
authors.affiliation: Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Eliana
authors.initials: E
authors.lastname: Saxon
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Luchansky
authors.forename: Howard C
authors.initials: HC
authors.lastname: Hang
authors.forename: Chong
authors.initials: C
authors.lastname: Yu
authors.forename: Sandy C
authors.initials: SC
authors.lastname: Lee
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Bertozzi
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D016466:CHO Cells / Q000378:metabolism; D019556:COS Cells / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D018922:HL-60 Cells; D006595:Hexosamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D010084:Oxidation-Reduction; D012794:Sialic Acids / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D001386:Azides; D006595:Hexosamines; D012794:Sialic Acids; D000117:Acetylglucosamine; C002022:N-acetylmannosamine