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dc.rights.licenseOpen Access
dc.contributor.authorCress, Brady F.
dc.contributor.authorBhaskar, Ujjwal
dc.contributor.authorVaidyanathan, Deepika
dc.contributor.authorWilliams, Asher
dc.contributor.authorCai, Chao
dc.contributor.authorLiu, Xinyue
dc.contributor.authorFu, Li
dc.contributor.authorM-Chari, Vandhana
dc.contributor.authorZhang, Fuming
dc.contributor.authorMousa, Shaker A.
dc.contributor.authorDordick, Jonathan S.
dc.contributor.authorKoffas, Mattheos A.G.
dc.contributor.authorLinhardt, Robert J.
dc.date2019
dc.date.accessioned2022-06-23T04:28:40Z
dc.date.available2022-06-23T04:28:40Z
dc.date.issued2019-04-23
dc.identifier.citationHeavy 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.
dc.identifier.issn15213773
dc.identifier.issn14337851
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5367
dc.identifier.urihttps://doi.org/10.1002/anie.201900768
dc.descriptionAngewandte Chemie, 58, 5962 –5966
dc.descriptionNote : 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.
dc.description.abstractHeparin 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.
dc.description.sponsorshipNational Science Foundation
dc.languageen_US
dc.language.isoENG
dc.publisherWiley
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofAngewandte Chemie - International Edition
dc.relation.urihttps://harc.rpi.edu/
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleHeavy heparin: A stable isotope-enriched, chemoenzymatically-synthesized, poly-component drug
dc.typeArticle
dcterms.accessRightsA full text version is available in DSpace@RPI
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.1002/anie.201900768
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pages5962-5966
rpi.description.volume58


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