Chemoenzymatic synthesis and lectin array characterization of a class of N-glycan clusters

J Am Chem Soc. 2009 Dec 16;131(49):17963-71. doi: 10.1021/ja9078539.

Abstract

N-Glycans are major components of many glycoproteins. These sugar moieties are frequently involved in important physiological and disease processes via their interactions with a variety of glycan-binding proteins (GBP). Clustering effect is an important feature in many glycan-lectin interactions. We describe in this paper a chemoenzymatic synthesis of novel N-glycan clusters using a tandem endoglycosidase-catalyzed transglycosylation. It was found that the internal beta-1,2-linked GlcNAc moieties in the N-glycan core, once exposed in the nonreducing terminus, was able to serve as acceptors for transglycosylation catalyzed by Endo-A and EndoM-N175A. This efficient chemoenzymatic method allows a quick extension of the sugar chains to form a class of glycan clusters in which sugar residues are all connected by native glycosidic linkages found in natural N-glycans. In addition, a discriminative enzymatic reaction at the two GlcNAc residues could be fulfilled to afford novel hybrid clusters. Lectin microarray studies revealed unusual properties in glyco-epitope expression by this panel of structurally well-defined synthetic N-glycans. These new compounds are likely valuable for functional glycomics studies to unveil new functions of both glycans and carbohydrate-binding proteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Catalysis
  • Lectins / chemistry*
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / chemistry*
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / metabolism
  • Polysaccharides / chemical synthesis*
  • Polysaccharides / chemistry
  • Polysaccharides / classification*
  • Protein Array Analysis

Substances

  • Lectins
  • Polysaccharides
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase