Nature Biotechnology21, 1343 - 1346 (2003)
Published online: 5 October 2003; | doi:10.1038/nbt885
Enzymatic synthesis of antithrombin III−binding heparan sulfate pentasaccharide
Balagurunathan Kuberan1, Miroslaw Z Lech1, David L Beeler1, Zhengliang L Wu1
& Robert D Rosenberg1, 2
1
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
2
Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Correspondence should be addressed to Robert D Rosenberg rdrrosen@mit.edu
Heparan sulfate (HS) proteoglycans are crucial to numerous biological processes and pathological conditions, but to date only a few HS structures have been synthesized and characterized with regard to structure-function relationships. Because HS proteoglycans are highly diverse in structure, there are substantial limitations on their synthesis by classical chemical means, and thus new methods to rapidly assemble bioactive HS structures are needed. Here we report the biosynthesis of bioactive HS oligosaccharides using an engineered set of cloned enzymes that mimics the Golgi apparatus in vitro. We rapidly and efficiently assembled the antithrombin III−binding pentasaccharide in just 6 steps, in contrast to the approximately 60 steps needed for its chemical synthesis, with an overall yield at least twofold greater and a completion time at least 100 times faster than for the chemical process.
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