Chemoenzymatic synthesis of heparin
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Authors
Dickinson, D.M.
Liu, J.
Linhardt, Robert J.
Issue Date
2015
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparan sulfate is a polysaccharide that plays essential physiological functions in the animal kingdom. Heparin, a highly sulfated form of heparan sulfate, is a widely prescribed anticoagulant drug worldwide. The heparan sulfate and heparin isolated from natural sources are highly heterogeneous mixtures differing in polysaccharide chain lengths and sulfation patterns. The access to structurally defined heparan sulfate and heparin is critically important to probe the contribution of specific sulfated saccharide structures to biological functions as well as for the development of the next generation of heparin-based anticoagulant drugs. The synthesis of heparan sulfate and heparin, using a purely chemical approach, has proven extremely difficult, especially for targets larger than octasaccharides having a high degree of site-specific sulfation. A new chemoenzymatic method has emerged as an effective alternative approach. This method utilizes recombinant heparan sulfate biosynthetic enzymes combined with unnatural uridine diphosphate-monosaccharide donors. Recent examples demonstrate the successful synthesis of ultra-low molecular weight heparin, low-molecular weight heparin and bioengineered heparin with unprecedented efficiency. The new method opens the opportunity to develop improved heparin-based therapeutics.
Description
Glycoscience: Biology and Medicine, N. Taniguchi, T. Endo, G. Hart, P. Seeberger, C. H. Wong (Eds.), Springer, pp 419-426
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Chemoenzymatic synthesis of heparin, D. M. Dickinson, J. Liu, R. J. Linhardt, Glycoscience: Biology and Medicine, N. Taniguchi, T. Endo, G. Hart, P. Seeberger, C.-H. Wong (Eds.), Springer, pp 419-426, 2015.
Publisher
Springer