Investigating the indentification and construction of therapeutic glycosaminoglycans

Beaudet, Julie Michele
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Linhardt, Robert J.
Dordick, Jonathan S.
McGown, Linda Baine
Dinolfo, Peter
Gilbert, Ryan
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Biochemistry and biophysics
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Using 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.
May 2013
School of Science
Biochemistry and Biophysics Program
Rensselaer Polytechnic Institute, Troy, NY
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