Date of Award
2024
Document Type
Campus Access Dissertation
Degree Name
Doctor of Philosophy in Chemistry (PhD)
Administrative Home Department
Department of Chemistry
Advisor 1
Marina Tanasova
Committee Member 1
Ashutosh Tiwari
Committee Member 2
Shiyue Fang
Committee Member 3
Smitha Rao
Abstract
The evident connection between metabolic diseases and metabolic alterations led to exploring alternative approaches for diagnosing, monitoring, and treating diseases, with a particular focus on metabolic reprogramming as a new therapeutic target. Metabolic reprogramming of carbohydrate uptake and metabolism is a widely recognized hallmark of cancer. Hence, the deregulations and alterations in the functioning of glucose transporters (GLUTs) as primary sugar transporters are common characteristics in various cancers, and they are currently being used to target cancers.
While the research on targeting glucose-transporting GLUTs dates back to the 1950s, fructose-specific GLUT5 and other non-specific fructose transporters have recently gained attention as potential targets for diagnostics and therapy. This shift is propelled by mounting evidence of the role that fructose plays in the development of a plethora of diseases, including cancer. Thus, targeting fructose transporters has emerged as a prominent strategy to deliver imaging and therapeutic agents specifically to cancer cells reliant on fructose for its development and progression.
Despite years of research, GLUTs’ targeting still faces challenges related to specificity, safety, and efficiency in both diagnostics and therapy. Therefore, novel tools allowing for molecular imaging of fructose-dependent cancers are needed. This dissertation introduces fluorescent imaging probes designed for applications in biomedical imaging. Those include the GLUT5-specific coumarin-based fluorescent probe compatible with PET (positron emission tomography) imaging. The work also showcases the advances toward GLUT-mediated delivery of larger fluorophores to broaden an array of fluorescence colors and fluorescence-based analytical tools for GLUT research. Specifically, this dissertation presents GLUT-specific rhodamine-based “turn-on” fluorescent probes, enabling imaging of GLUT activity in live cells and in vivo. The outcomes of this work provide critical insight into GLUT substrate specificity and substrate binding vs. passage, establishing the basis for designing more specific and effective activity and expression probes for GLUTs. Overall, the developed imaging agents reported in this dissertation offer additional functionalities, contributing to the existing repertoire of molecular tools for imaging and distinguishing fructose-dependent cancer cells. This work lays the foundation for further rational design of GLUT-specific probes with desired properties.
Recommended Citation
Oronova, Adelina, "Small Fluorescent Glycoconjugates as Imaging Agents for GLUT Sugar Transporters", Campus Access Dissertation, Michigan Technological University, 2024.
https://digitalcommons.mtu.edu/etdr/1705