Synthesis and Biological Investigation of Membrane-targeting Antimicrobials Público
Dekarske, Madeline (Summer 2022)
Abstract
Experts currently think of antibiotic resistance as a second, “silent” pandemic. The Centers for Disease Control and Prevention released a report in 2019 about their efforts to stymie bacterial resistance to current antibiotics and now detail that the COVID-19 pandemic will likely decrease the progress previously attained. Thus, in this battle of constant bacterial evolution and development of resistance, we require new tools to better combat antibiotic resistance. During my time in the Wuest Lab, I have worked on three projects that center around fighting resistance. One project was a medicinal chemistry collaboration, in which we made nTZDpa derivatives in order to combat not only Staphylococcus aureus resistance but also persistence. Another focused on a biology collaboration, in which we investigated how C2 affects planktonic Streptococcus mutans, the primary pathogenic agent in the oral microbiome. I also designed a project centered around the ogipeptins, a class of macrocyclic peptides, with selective Gram-negative activity and crafted syntheses and a mechanism of action hypothesis
Table of Contents
Chapter 1: Overview of Antibiotic Resistance……………………………………………………..……1
Chapter 2: nTZDpa………………………………………………………………………..……………......22
Chapter 3: Honokiol……………………………………………………………………………………......46
Chapter 4: Ogipeptins…………………………………………………………………………………......64
Chapter 5: Supplementary Information…………...………………………………………………….101
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