Heavy heparin: A stable isotope-enriched, chemoenzymatically-synthesized, poly-component drug

Authors
Cress, Brady F.
Bhaskar, Ujjwal
Vaidyanathan, Deepika
Williams, Asher
Cai, Chao
Liu, Xinyue
Fu, Li
M-Chari, Vandhana
Zhang, Fuming
Mousa, Shaker A.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2019-04-23
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Full Citation
Heavy heparin: A stable isotope-enriched, chemoenzymatically-synthesized, poly-component drug, B. F. Cress, U. Bhaskar, D. Vaidyanathan, A. Williams, C. Cai, X. Liu, L. Fu, V. M-Chari, F. Zhang, S. A. Mousa, J. S. Dordick, M. A. G. Koffas, R. J. Linhardt, Angewandte Chemie, 58, 5962 –5966, 2019.
Abstract
Heparin is a highly sulfated, complex polysaccharide and widely used anticoagulant pharmaceutical. In this work, we chemoenzymatically synthesized perdeuteroheparin from biosynthetically enriched heparosan precursor obtained from microbial culture in deuterated medium. Chemical de-N-acetylation, chemical N-sulfation, enzymatic epimerization, and enzymatic sulfation with recombinant heparin biosynthetic enzymes afforded perdeuteroheparin comparable to pharmaceutical heparin. A series of applications for heavy heparin and its heavy biosynthetic intermediates are demonstrated, including generation of stable isotope labeled disaccharide standards, development of a non-radioactive NMR assay for glucuronosyl-C5-epimerase, and background-free quantification of in vivo half-life following administration to rabbits. We anticipate that this approach can be extended to produce other isotope-enriched glycosaminoglycans.
Description
Angewandte Chemie, 58, 5962 –5966
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Wiley
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Angewandte Chemie - International Edition
https://harc.rpi.edu/
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