Date of Award

2020

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Administrative Home Department

Department of Chemistry

Advisor 1

Marina Tanasova

Committee Member 1

Shiyue Fang

Committee Member 2

Tarun Dam

Committee Member 3

Smitha Rao

Abstract

Carbohydrate Transporters (GLUTs) are responsible for the transportation of sugars into the cell and have been of great interest in research for decades. Alterations or mutations that result in overexpression of GLUTs have been linked to a great number of diseases including, obesity, diabetes, and cancer. Differentiation between transporters has been shown to be incredibly difficult due to the highly conserved nature of the transporter structure, and thus specific targeting of transporters has proven a difficult challenge. Additionally, the GLUTs have been shown to high flexibility in their conformations, so it is difficult to determine what can or cannot pass through the transporter, which has led to many failed attempts at targeting these transporters. So in an attempt to gain a better understanding of one transporter specifically, GLUT 5, a transporter known to be responsible for fructose transporter, new probes were created by conjugating 1-amino-2,5-anhydro-D-mannitol and various fluorescent coumarins. The probes were tested in both normal and cancerous cell lines in order to determine their uptake kinetics and transport specificity. To establish transport specificity the probes were tested in the presence of various competitive and noncompetitive inhibitors. The probe transport was analyzed through various meanings including microplate setting, immunostaining, and confocal microscopy. The combined analysis of the probes has shown to be GLUT5 specific which allows for their use as for biochemical and biomedical imaging an analysis of GLUT5 transporter in cells.

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