Show simple item record

dc.rights.licenseRestricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.
dc.contributorLinhardt, Robert J.
dc.contributorMcGown, Linda Baine
dc.contributorBailey, R. A. (Ronald Albert), 1933-
dc.contributor.authorHarvey, Catherine Malinda
dc.date.accessioned2021-11-03T08:02:01Z
dc.date.available2021-11-03T08:02:01Z
dc.date.created2014-01-16T11:26:42Z
dc.date.issued2013-08
dc.identifier.urihttps://hdl.handle.net/20.500.13015/949
dc.descriptionAugust 2013
dc.descriptionSchool of Science
dc.description.abstractHeparin is a highly sulfated glycosaminoglycan; a heterogeneous polysaccharide that exhibit anticoagulant activity. The commercial drug, Arixtra (fondaparinux sodium), is a structurally homogeneous heparin pentasaccharide (an ultralow molecular weight heparin). The current chemical synthesis is rather lengthy (≈50 steps) and low-yielding (<1%). A promising alternative approach developed by our laboratory and others is to chemoenzymatically synthesize heparins utilizing both uridine diphosphate sugars as electrophilic donors and the para-nitrophenyl β-glucuronide as the initial nucleophilic acceptor; this commercially available monosaccharide acceptor is conformable to enzymatic elongation, conducive to the purification of these oligosaccharides with a C-18 column, and cleavable with ceric ammonium sulfate. Fondaparinux synthesis requires a backbone structure of defined size that can be specifically N-sulfonated and selectively modified by the heparan sulfate sulfotransferases and C5-epimerase. This thesis describes efforts to chemoenzymatically synthesize heparan sulfate oligosaccharide backbones, key intermediates in the synthesis of an Arixtra analog.
dc.language.isoENG
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.subjectChemistry
dc.titleChemoenzymatic synthesis of heparin oligosaccharides
dc.typeElectronic thesis
dc.typeThesis
dc.digitool.pid170017
dc.digitool.pid170018
dc.digitool.pid170019
dc.rights.holderThis electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
dc.description.degreeMS
dc.relation.departmentDept. of Chemistry and Chemical Biology


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record