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dc.rights.licenseRestricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.
dc.contributorLinhardt, Robert J.
dc.contributorDordick, Jonathan S.
dc.contributorMcGown, Linda Baine
dc.contributorDinolfo, Peter
dc.contributorGilbert, Ryan
dc.contributor.authorBeaudet, Julie Michele
dc.date.accessioned2021-11-03T07:59:01Z
dc.date.available2021-11-03T07:59:01Z
dc.date.created2013-09-09T14:42:03Z
dc.date.issued2013-05
dc.identifier.urihttps://hdl.handle.net/20.500.13015/867
dc.descriptionMay 2013
dc.descriptionSchool of Science
dc.description.abstractUsing the heparin biosynthetic pathway as a model, three small-scale techniques were tested: milligram bench-top synthesis, channel microfluidics via SPR, and digital microfluidics. The target structure was a specific pentasaccharide which gives heparin its anticoagulant properties. Out of the three techniques, only the product synthesized using SPR was confirmed to have the desired sequence. This is likely due to the temperature control, detection sensitivity, and lack of manual handling provided by the instrument. However this technique is not ideal for testing many different potential targets. Therefore it is necessary to continue to improve the protocols used for the chemoenzymatic synthesis of GAGs and the techniques used to produce them. Using kinetic data regarding the binding affinity of physical characteristics in natural interactions when selecting and constructing potential therapeutic targets will expose new options for pharmaceuticals. Accurate and efficient microscale chemoenzymatic synthesis protocols will side in the screening of these options and eventual production.
dc.description.abstractGlycosaminoglycans (GAGs) are linear, negatively charged polysaccharides. They are involved in scores of physiological interactions ranging from cell communication to lipid transport to blood anticoagulation. For this reason, they are prime candidates for pharmaceutical targets. However glycosaminoglycans can vary significantly in size and sulfonation so it is necessary to investigate binding interactions carefully when evaluating interactions for target GAG specifications. Protein-GAG interactions can be measured using surface plasmon resonance (SPR). SPR measures the interaction of a protein analyte with an immobilized ligand. A variety of experimental conditions exist to gather quantitative and qualitative interaction data.
dc.description.abstractOnce kinetic data has been collected it can be used to appraise potential targets based on the size, sulfonation, and baseline kinetic rates. Targets can be graded using SPR or other analytical techniques. A popular technique in drug discovery is the use of microarrays. These arrays call for dozens of constructs to be evaluated at once. Pure chemical synthesis of GAGs is expensive in time and materials. Chemoenzymatic synthesis is a much more economical route but without a `glycomic code' comparable to that of genetics, enzymatic synthesis can be difficult to control.
dc.language.isoENG
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.subjectBiochemistry and biophysics
dc.titleInvestigating the indentification and construction of therapeutic glycosaminoglycans
dc.typeElectronic thesis
dc.typeThesis
dc.digitool.pid167109
dc.digitool.pid167110
dc.digitool.pid167111
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.degreePhD
dc.relation.departmentBiochemistry and Biophysics Program


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