Designing a Reactive Warhead to Bind and Inhibit Pseudomonas aeruginosa’s Periplasmic Protein, Inhibitor of Vertebrate Lysozyme
Pseudomonas aeruginosa 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 P. aeruginosa, it is becoming increasingly more challenging to treat an infection by traditional means. Further complicating treatment, P. aeruginosa 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 P. aeruginosa 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.
pseudomonas aeurginosa, inhibitor of vertebrate lysozyme, nuclear magnetic resonance, rhenium tricarbonyl, Biochemistry, Biophysics, Chemistry
Networked Digital Library of Theses and Dissertations