Evaluation of Biological Signaling and Transport Molecules Using Synthetic, Computational, and Mass Spectrometric Techniques.
Date of Award
Doctor of Philosophy
Shawn R. Campagna
Tessa R. Calhoun, Michael D. Best, Gladys Alexandre
There are many unanswered questions at the molecular level of biology, and a chemical approach is most often necessary to answer those questions. A chemical approach in this instance is a combination of synthetic organic chemistry, analytical chemistry, and computational chemistry. Three unrelated projects will be discussed in this document, which utilize a combination of chemical tools to make sense of what is happening at the molecular level in these systems. Each of the projects described in this dissertation rely on my abilities as an analytical and organic chemist to propose substantiated hypotheses on molecular feature, structure, and biological function. I believe that through this work, progress has been made to better understand the chemical knowledge of these systems for future investigations.Chapter 1 will address drug-induced diabetes, which is a condition that is usually brought on from treatment of inflammation with glucocorticoids; Although these drugs are powerful anti-inflammatory agents, they have a propensity to hinder the secretion of insulin from pancreatic β [beta]-cells. To address this issue, a library of glucocorticoid analogues exhibiting a non-steroidal scaffold were synthesized, characterized, computationally modeled, and tested in-vitro as anti-inflammatory drug candidates with little to no effect on insulin production.Chapter 2 focuses on an isotope tracing experiment using synthetic lipids to differentiate straight-chain lipid species from isobaric congeners containing a terminal isopropyl moiety. This was devised to investigate plausible semiochemicals in Myxococcus xanthus towards a developmental phenotype initiated by an unknown lipid potentially containing this motif. This method has several implications in lipidomic and metabolomic analyses of biological systems, being that these isobars are impossible to distinguish from one another without analytical standards.Chapter 3 is an investigation of microbial iron-sequestration, which is essential for nearly all life forms but is of particular interest in marine microbes. Many microbes use specialized molecules known as siderophores to capture iron from the environment to use for several life-sustaining functions. This final chapter spotlights the use of chromatographic and mass spectrometric techniques to investigate uncharacterized siderophores isolated from the marine bacterium S. loktanella sp. SE62.
Kennedy, Brandon James, "Evaluation of Biological Signaling and Transport Molecules Using Synthetic, Computational, and Mass Spectrometric Techniques.. " PhD diss., University of Tennessee, 2019.
Portions of this document will be part of future publications