Author
Cress, Brady F.; Bhaskar, Ujjwal; Vaidyanathan, Deepika; Williams, Asher; Cai, Chao; Liu, Xinyue; Fu, Li; M-Chari, Vandhana; Zhang, Fuming; Mousa, Shaker A.; Dordick, Jonathan S.; Koffas, Mattheos A.G.; Linhardt, Robert J.
Other Contributors
Date Issued
2019-04-23
Subject
Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
Degree
Terms of Use
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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; 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);
Publisher
Wiley
Relationships
The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; Angewandte Chemie - International Edition; https://harc.rpi.edu/;
Access
Open Access; A full text version is available in DSpace@RPI;