Modified GM3 gangliosides produced by metabolic oligosaccharide engineering

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Whitman, Chad M.^1,2  Yang, Fan¹  Kohler, Jennifer J.¹ 

[1] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Translat Res, Dallas, TX 75390 USA

[2] Stanford Univ, Dept Chem, Stanford, CA 94305 USA

关键词: Ganglioside;    Sialic acid;    Diazirine;    Sialyltransferase;    Metabolic engineering;   

DOI  :  10.1016/j.bmcl.2011.04.128

来源: Elsevier

【 摘 要 】

Metabolic oligosaccharide engineering is powerful approach to altering the structure of cellular sialosides. This method relies on culturing cells with N-acetylmannosamine (ManNAc) analogs that are metabolized to their sialic acid counterparts and added to glycoproteins and glycolipids. Here we employed two cell lines that are deficient in ManNAc biosynthesis and examined their relative abilities to metabolize a panel of ManNAc analogs to sialosides. In addition to measuring global sialoside production, we also examined biosynthesis of the sialic acid-containing glycolipid, GM3. We discovered that the two cell lines differ in their ability to discriminate among the variant forms of ManNAc. Further, our data suggest that modified forms of sialic acid may be preferentially incorporated into certain sialosides and excluded from others. Taken together, our results demonstrate that global analysis of sialoside production can obscure sialoside-specific differences. These findings have implications for downstream applications of metabolic oligosaccharide engineering, including imaging and proteomics. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

Free