Investigating Cellular Metabolism of Synthetic Azidosugars with the Staudinger Ligation

• Published in: Journal of the American Chemical Society 2002-12, Vol.124 (50), p.14893-14902
• Main Authors: Saxon, Eliana, Luchansky, Sarah J, Hang, Howard C, Yu, Chong, Lee, Sandy C, Bertozzi, Carolyn R
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - analogs & derivatives; Acetylglucosamine - chemical synthesis; Acetylglucosamine - metabolism; Animals; Azides - chemical synthesis; Azides - chemistry; Azides - metabolism; Biological and medical sciences; Biomimetic Materials - chemistry; Biomimetic Materials - metabolism; Cell Membrane - metabolism; CHO Cells - metabolism; COS Cells - metabolism; Cricetinae; Fundamental and applied biological sciences. Psychology; Hexosamines - chemical synthesis; Hexosamines - chemistry; Hexosamines - metabolism; HL-60 Cells; Humans; Jurkat Cells - metabolism; Molecular and cellular biology; Oxidation-Reduction; Sialic Acids - biosynthesis; Sialic Acids - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja027748x

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.