Investigating cellular metabolism of synthetic azidosugars with the Staudinger ligation.
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.
Saxon
Eliana
E
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, CA 94720, USA.
Luchansky
Sarah J
SJ
Hang
Howard C
HC
Yu
Chong
C
Lee
Sandy C
SC
Bertozzi
Carolyn R
CR
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
D001386:Azides; D006595:Hexosamines; D012794:Sialic Acids; D000117:Acetylglucosamine; C002022:N-acetylmannosamine