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Chem Biol. 2007 Sep;14(9):986-93.

Using an enzymatic combinatorial approach to identify anticoagulant heparan sulfate structures.

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  • 1Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

Heparan sulfate (HS) represents a major class of glycans that perform central physiological functions. Emerging HS and glycosaminoglycan microarray techniques are used to interrogate the structure and function relationship to develop novel therapeutic agents. Availability of HS with specific sulfation patterns has been a limiting factor and impedes the accuracy of HS glycomics studies. Although organic synthesis provides oligosaccharides, these may not fully represent the biological functions of polysaccharides. Here, we present a study for developing an enzyme-based approach to synthesize a polysaccharide library with different sulfation patterns. Using different combinations of biosynthetic enzymes, we synthesized eight unique polysaccharides. We discovered that polysaccharides without the iduronic acid residue displayed strong binding affinity to antithrombin and high anti-Xa and anti-IIa activities. The enzyme-based synthetic approach could become a general method for discovering new HS structures with unique biological functions.

PMID:
17884631
[PubMed - indexed for MEDLINE]
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