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Investigations of the biological effects of natural products on metal-mediated metabolic disease states

Abstract

Metabolic disease states like diabetes, Wilson disease, and Menkes disease are linked to dysregulation of d-block metals in the body, and current therapeutic approaches aim to alter these metal populations. Natural products often serve as inspiration for the development of therapeutics due to their inherent bioactivity. This thesis describes investigations of the interactions between natural products and metal ions in the context of affecting metabolic disease states. Chapter 1 introduces the importance of micronutrients in human biology, highlights disease states associated with metal dysregulation, and finally outlines analytical tools and methods used to study bioinorganic systems. Chapter 2 provides a deeper analysis of the connections between plant-derived molecules, metal ions, and metabolic disease states while proposing further study for potential therapeutic uses. Chapters 3 and 4 outline investigations of the interactions of copper with specific plant-derived molecules, flavonoids and rice bran protein hydrolysates, respectively. Studies in controlled solutions provide a basis for further analyses of the downstream biological effects in model systems. Chapter 5 highlights NMR method and application development towards studying the cobalt center of vitamin B12 with different binding partners. Finally, chapter 6 presents a copper-dependent inhibition of bioluminescence in marine systems due to an oxidation of the luciferin substrates.

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