Date of Award
May 2021
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
Committee Member
Kristi J. Whitehead
Committee Member
Dev P. Arya
Committee Member
Carlos D. Garcia
Committee Member
Ya-Ping Sun
Abstract
Recent advances in technology have given scientists various tools to further investigate the vast microbiological communities occupying virtually every portion of our anatomy in attempts to better understand their impact on our overall health. Within the gut, where the largest community of microorganisms reside, researchers have observed specific changes to the composition of this community correlate with the onset of several disease states endemic worldwide. In efforts to address these microbiological shifts, our lab is interested in exploring a small molecule-based strategy to induce targeted shifts to the gastrointestinal microbiota for therapeutic gain. Our previous research has established that the α-glucosidase inhibitory compound acarbose is capable of arresting of the polysaccharide metabolism of the Bacteroides, a genus of bacteria that has been implicated in the initial onset of Type 1 diabetes in genetically at-risk individuals. In continuation of these efforts, we sought to explore new molecular scaffolds that exhibit similar activity as acarbose and evaluate their potential to selectively disrupt the growth the Bacteroides spp. while maintaining minimal effects on other gut microbes. These efforts included the synthesis of a library of compounds incorporating 1,2,3-triazoles into the structure of various monosaccharides, yet after a thorough investigation into their activity, these compounds were found to display little growth disruption against B. thetaiotaomicron, a common model organism representing the Bacteroides genus. These results prompted our development of an activity-based protein profiling strategy poised at providing a better understanding of the nuanced interactions our initial hit molecule, acarbose, imparts on these microbes. In our preliminary study, we found that an acarbose derivative retains similar activity as its parent compound against B. thetaiotaomicron, a key step in the successful application of this methodology. In addition to these efforts, this document discloses the progress made toward the development of promising anti-parasitic compounds aimed at inhibiting the heme metabolism of Toxoplasma gondii, a prolific parasite capable of infecting virtually all warm blooded organisms. Finally, the last chapter of this document reports on a new substrate scope aimed at probing the activity of our developed peptide-based hypervalent iodine catalytic system for use in the α-oxytosylation of ketones.
Recommended Citation
Rees, Kerrick Connor, "Progress Toward the Development of Inhibitory Small Molecules for the Bacteroides and Toxoplasma Microorganisms" (2021). All Dissertations. 2803.
https://open.clemson.edu/all_dissertations/2803