Combinatorial one-pot chemoenzymatic synthesis of heparin
Authors
Bhaskar, Ujjwal
Li, Guoyun
Fu, Li
Onishi, Akihiro
Suflita, Mathew
Dordick, Jonathan S.
Linhardt, Robert J.
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2015-05-20
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Combinatorial one-pot chemoenzymatic synthesis of heparin, U. Bhaskar, G. Li, L. Fu, A. Onishi, M. Suflita, J. S. Dordick, R. J. Linhardt, Carbohydrate Polymers, 122, 399–407, 2015.
Abstract
Contamination in heparin batches during early 2008 has resulted in a significant effort to develop a safer bioengineered heparin using bacterial capsular polysaccharide heparosan and recombinant enzymes derived from the heparin/heparan sulfate biosynthetic pathway. This requires controlled chemical N-deacetylation/N-sulfonation of heparosan followed by epimerization of most of its glucuronic acid residues to iduronic acid and O-sulfation of the C2 position of iduronic acid and the C3 and C6 positions of the glucosamine residues. A combinatorial study of multi-enzyme, one-pot, in vitro biocatalytic synthesis, carried out in tandem with sensitive analytical techniques, reveals controlled structural changes leading to heparin products similar to animal-derived heparin active pharmaceutical ingredients. Liquid chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy analysis confirms an abundance of heparin's characteristic trisulfated disaccharide, as well as 3-O-sulfo containing residues critical for heparin binding to antithrombin III and its anticoagulant activity. The bioengineered heparins prepared using this simplified one-pot chemoenzymatic synthesis also show in vitro anticoagulant activity.
Description
Carbohydrate Polymers, 122, 399–407
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.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Elsevier
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Carbohydrate Polymers
https://harc.rpi.edu/
Rensselaer Polytechnic Institute, Troy, NY
Carbohydrate Polymers
https://harc.rpi.edu/
Access
A full text version is available in DSpace@RPI