Investigating cellular metabolism of synthetic azidosugars with the Staudinger ligation

被引:243
作者
Saxon, E
Luchansky, SJ
Hang, HC
Yu, C
Lee, SC
Bertozzi, CR [1 ]
机构
[1] Univ Calif Berkeley, Dept Chem, Ctr New Direct Organ Synth, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Ctr New Direct Organ Synth, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Ctr Adv Mat, Berkeley, CA 94720 USA
[4] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
关键词
D O I
10.1021/ja027748x
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:14893 / 14902
页数:10
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