Enzymatic Placement of 6-O-Sulfo Groups in Heparan Sulfate

Renpeng Liu and Jian Liu*
Division of Medicinal Chemistry and Natural Products, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States
Biochemistry, 2011, 50 (20), pp 4382–4391
DOI: 10.1021/bi200072t
Publication Date (Web): April 20, 2011
Copyright © 2011 American Chemical Society
*Room 303, Beard Hall, University of North Carolina, Chapel Hill, NC 27599. Telephone: (919) 843-6511. Fax: (919) 843-5432. E-mail: jian_liu@unc.edu.

  Funding Statement

This work is supported in part by National Institutes of Health Grants AI50050, HL094463, and AI074775.

Abstract

Abstract Image

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.

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History

  • Published In Issue May 24, 2011
  • Article ASAPMay 02, 2011
  • Just Accepted ManuscriptApril 20, 2011
  • Received: January 17, 2011
    Revised: March 25, 2011

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