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Glycans for ricin and Shiga toxins: Synthesis and biophysical characterization

Mahajan, Sujit S.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307320080

Abstract Details

2011, PhD, University of Cincinnati, Arts and Sciences: Chemistry.
Recent health emergencies concern everybody in the wake of outbreaks of bacterial and viral infections as well as acts of bioterrorism. Health and safety of common man should be and is the top priority for any research organization and government agency. The critical step is to take preventive actions before the disaster strikes, which will in turn be effective in controlling the hazard. Currently, various infectious agent detection systems available in the market use different detecting elements like DNA, aptamers, and antibodies. However, these motifs are expensive and face problems such as robustness and stability under normal temperatures in the field. These relatively less explored recognition elements can provide a solution to the limitations of commercial sensors/detection systems. Glycan microarrays are getting the recognition in order to develop commercial detection systems based on glycans. The cell surface glycans are the natural receptors for different pathogens and viruses. One can achieve the selectivity for different infectious agents by synthesizing and tailoring appropriate glycans. In addition, molecular-level study of the glycan-pathogen interactions is an essential parameter in understanding interactions occurring at cellular level. The long term goal of our research involves understanding the interdependent factors which affect glycan-protein binding and developing handheld biosensors which can be used to detect selective pathogens instantaneously. In present study, we have synthesized a library of high- affinity multivalent glycans for detection of ricin toxin and Shiga toxins (Stxs). Ricin is a plant-originated toxin, which can be used as potential biothreat agent while Shiga toxin 2 or Stx2 is a strain which causes a kidney related disease, hemolytic uremic syndrome (HUS). We performed the binding specificity studies using biophysical characterization techniques such as enzyme linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR). We studied the effect of different factors (such as structure, density, and presentation of glycans) responsible for the protein-glycan binding using the ß-galactoside analogues with ricin toxin. We also synthesized Pk-saccharide analogues to study unimolecular binding with Stx variants. In a collaborative research, we also studied the binding specificities of different glycans for Shiga toxin variants across different platforms. We expressed and purified the Stx-B subunits used in the Stx binding studies. The results obtained in these studies are expected to define a set of rules which can be used to generate high affinity ligands, which in turn will lead to effective diagnostics and therapeutics for the infectious agents.
Suri Iyer, PhD (Committee Chair)
H Brian Halsall, PhD (Committee Member)
David Smithrud, PhD (Committee Member)
Alison Weiss, PhD (Committee Member)
407 p.
Chemistry
glycan; ricin; Shiga; microarray; toxins; detection

Recommended Citations

Citations

  • Mahajan, S. S. (2011). Glycans for ricin and Shiga toxins: Synthesis and biophysical characterization [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307320080

    APA Style (7th edition)

  • Mahajan, Sujit. Glycans for ricin and Shiga toxins: Synthesis and biophysical characterization. 2011. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307320080.

    MLA Style (8th edition)

  • Mahajan, Sujit. "Glycans for ricin and Shiga toxins: Synthesis and biophysical characterization." Doctoral dissertation, University of Cincinnati, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1307320080

    Chicago Manual of Style (17th edition)

ucin1307320080
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© 2011, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.