Enzymatic placement of 6-O-sulfo groups in heparan sulfate

Biochemistry. 2011 May 24;50(20):4382-91. doi: 10.1021/bi200072t. Epub 2011 May 2.

Abstract

Heparan sulfate is a highly sulfated polysaccharide that exhibits important physiological and pathological functions. The glucosamine residue of heparan sulfate can carry sulfo groups at the 2-N, 3-O, and 6-O positions, leading to diverse polysaccharide structures. 6-O-Sulfation at the glucosamine residue contributes to a wide range of biological functions. Here, we report a method for controlling the positioning of 6-O-sulfo groups in oligosaccharides. This was achieved by synthesizing oligosaccharide backbones from a disaccharide building block utilizing glycosyltransferases followed by modifications using heparan sulfate N-sulfotransferase and 6-O-sulfotransferases. This method offers a viable approach for preparing heparan sulfate oligosaccharides with precisely located 6-O-sulfo groups.

Publication types

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

MeSH terms

  • Carbohydrate Sequence
  • Escherichia coli / enzymology
  • Feasibility Studies
  • Heparitin Sulfate / chemistry*
  • Heparitin Sulfate / metabolism*
  • Molecular Sequence Data
  • Oligosaccharides / chemical synthesis
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism
  • Pasteurella multocida / enzymology
  • Structure-Activity Relationship
  • Substrate Specificity
  • Sulfates / chemistry
  • Sulfates / metabolism
  • Transferases / metabolism*

Substances

  • Oligosaccharides
  • Sulfates
  • Heparitin Sulfate
  • Transferases