Enzymatic Synthesis of Glycosaminoglycan Heparin

Robert J. Linhardt; Jonathan S. Dordick; Paul L. Deangelis; Jian Liu

doi:10.1055/s-2007-982076

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2007; 33(5): 453-465
DOI: 10.1055/s-2007-982076

Enzymatic Synthesis of Glycosaminoglycan Heparin

Robert J. Linhardt¹ , Jonathan S. Dordick² , Paul L. Deangelis² , Jian Liu¹

¹Departments of Chemistry and Chemical Biology, Chemical and Biological Engineering, and Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York
²Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
³Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Abstract

ABSTRACT

Heparin and its low molecular weight heparin derivatives, widely used as clinical anticoagulants, are acidic polysaccharide members of a family of biomacromolecules called glycosaminoglycans (GAGs). Heparin and the related heparan sulfate are biosynthesized in the Golgi apparatus of eukaryotic cells. Heparin is a polycomponent drug that currently is prepared for clinical use by extraction from animal tissues. A heparin pentasaccharide, fondaparinux, has also been prepared through chemical synthesis for use as a homogenous anticoagulant drug. Recent enabling technologies suggest that it may now be possible to synthesize heparin and its derivatives enzymatically. Moreover, new technologies including advances in synthetic carbohydrate synthesis, enzyme-based GAG synthesis, micro- and nano-display of GAGs, rapid on-line structural analysis, and microarray/microfluidic technologies might be applied to the enzymatic synthesis of heparins with defined structures and exhibiting selected activities. The advent of these new technologies also makes it possible to consider the construction of an artificial Golgi to increase our understanding of the cellular control of GAG biosyntheses in this organelle.

KEYWORDS

Heparin - enzymes - biosynthesis - Golgi - microfluidics

Full Text

References

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Robert J LinhardtPh.D.

Departments of Chemistry and Chemical Biology, Chemical and Biological Engineering, and Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute

110 8th Street, Troy, NY 12180

Email: linhar@rpi.edu