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Physical Sciences and Mathematics

University of the Pacific

Theses/Dissertations

2024

Chemistry

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Structural And Functional Studies Of The Human Members Of The Macrophage Migration Inhibitory Factor Family, Andrew Parkins Jan 2024

Structural And Functional Studies Of The Human Members Of The Macrophage Migration Inhibitory Factor Family, Andrew Parkins

University of the Pacific Theses and Dissertations

Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (D-DT) are the two human members of the MIF superfamily, which are implicated in an array of autoimmune disorders, inflammatory diseases, and cancer via their pleiotropic functionality. Despite only sharing 34% sequence identity, MIF and D-DT have high structural homology and overlapping functional traits, including activation of the type II cell surface receptor CD74 and keto-enol tautomerase activity. The MIF and/or D-DT-induced activation of CD74 leads to signaling cascades pivotal for cell growth, proliferation, and inhibition of apoptosis. Such characteristics make MIF and D-DT attractive molecular targets for drug discovery.

Currently, all …


Synthesis Of Hydroxycinnamate Derivatives And Characterization Of Bioactivity As Radical Scavengers And Α-Glucosidase Inhibitors, Cate Simmermaker Jan 2024

Synthesis Of Hydroxycinnamate Derivatives And Characterization Of Bioactivity As Radical Scavengers And Α-Glucosidase Inhibitors, Cate Simmermaker

University of the Pacific Theses and Dissertations

Hydroxycinnamic acids (HCAs), a class of polyphenols commonly found in regularly consumed fruits and vegetables, have been investigated for efficacy as radical scavengers and glycosidase inhibitors. These compounds could mitigate the negative health effects of free radicals in oxidative stress diseases including neurodegeneration, cancer and diabetes. The HCAs investigated were caffeic acid (1), p-coumaric acid (2), ferulic acid (3), and sinapic acid (4). The compounds were derivatized with synthetically prepared amino acid esters through a four-step synthesis including protective acetylation, chlorination of the carboxylic acid, amidation, and subsequent deprotection of all applied protecting groups. The inclusion of diverse derivative groups …