Designing a Reactive Warhead to Bind and Inhibit Pseudomonas aeruginosa’s Periplasmic Protein, Inhibitor of Vertebrate Lysozyme

<p><em>Pseudomonas aeruginosa</em> is a Gram-negative bacterium commonly found throughout the environment. It is a significant cause of disease and mortality in immunodeficient patients such as those suffering from cystic fibrosis (CF). Due to the emerging antibiotic resistance of <em>P. aeruginosa</em>, it is becoming increasingly more challenging to treat an infection by traditional means. Further complicating treatment, <em>P. aeruginosa</em> secretes a protein known as Inhibitor of Vertebrate Lysozyme (PaIVY) that binds to and inhibits C-type lysozyme, thus preventing the degradation of the bacterium. A reactive chemical warhead was synthesized from a rhenium(I) tricarbonyl derivative inorder to bind to and irreversibly inhibit PaIVY, thereby allowing endogenous host lysozyme to effectively degrade drug-resistant <em>P. aeruginosa</em> bacteria. Various biophysical methods, such as fluorescence spectroscopy, NMR, and mass spectrometry are utilized in the characterization of the rhenium(I) tricarbonyl derivative and the binding interaction PaIVY experiences when placed in the presence of the chemical warhead. </p>

Name thesis:degree_name

Master of Science in Chemical Sciences (MSCB)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2021

Author dc:creator

• Greinke, Leah

Contributors dc:contributor

• Thomas C. Leeper
• Janet Shaw
• Scott Nowak

• pseudomonas aeurginosa
• inhibitor of vertebrate lysozyme
• nuclear magnetic resonance
• rhenium tricarbonyl
• Biochemistry
• Biophysics
• Chemistry

Repository record dc:identifier

https://digitalcommons.kennesaw.edu/mscs_etd/36

OAI identifier oai:identifier

oai:digitalcommons.kennesaw.edu:mscs_etd-1038