Date of Award

Fall 12-3-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Dr. Suri. S. Iyer

Second Advisor

Dr Kathyrn Grant

Third Advisor

Dr George Wang

Fourth Advisor

Dr Gangli Wang

Abstract

Glycans are present on the cell surface of mammalian cells. In Dr. Iyer’s laboratories, we aim to understand the interactions of cell surface glycans with toxins and pathogens at a molecular level and use that information to develop a point of care diagnostics.

The focus is on the development of a novel electrochemical assay that uses repurposed glucose meters for the detection of different analytes. The released glucose can be detected using personal glucose meters. One major concern is that of background glucose present in blood and other matrices. To eliminate the effect of background glucose, we have developed an electrochemical assay to detect other molecules such as paracetamol or catechol in the presence of large amounts of glucose. The strips used for the assay were devoid of glucose oxidase or glucose dehydrogenase, and hence, glucose cannot get oxidized and will not pose a problem. The paracetamol/catechol gets oxidized directly on the surface of the strips and can be detected directly. This assay was used to detect enzymes, influenza viruses, S. pneumoniae, and E. coli.

We further worked on an immunoassay-based detection method for influenza virus. Biotinylated bivalent Zanamivir analogs as probes for influenza viruses were designed and synthesized. The compound was used in a “glycan” based sandwich assay; where glycans were immobilized on glass slides to capture strains of Influenza A H1N1, A/Brisbane/59/2007 virus and the biotinylated bivalent Zanamivir analog-labeled streptavidin complex was used as a reporter. This study indicated that glycans could be used for capturing and reporting influenza viruses and the biotinylated compounds could be used as probes for capturing and isolating influenza viruses from complex mixtures.

We next expanded the innovative concept to develop assays for blood disorders. We synthesized of peptide substrates bearing electrochemically inactive molecules are required. We have designed a substrate that can directly measure the amount of thrombin in blood and the doctors can use this to adjust the dosage of anti-coagulants prescribed for high-risk patients. These compounds will be eventually used to develop assays that could potentially be used to monitor oral anticoagulant therapies and patients taking recombinant blood coagulation factors.

DOI

https://doi.org/10.57709/13452753

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