AMR Completed Master's Thesis 2021.pdf (1.5 MB)
Synthesis of a Cationic Amphiphilic Polyproline Helix (CAPH) Conjugate with Polymyxin B
Pathogens such as Listeria, Shigella, Brucella, Salmonella, Mycobacterium tuberculosis and
methicillin-resistant Staphylococcus aureus (MRSA) can traverse into mammalian cells, such as
phagocytic macrophages. Once inside, these bacteria can survive and reproduce, causing chronic
infections. It is of utmost importance to develop novel antibiotics with broad spectrum activity to
control these deadly bacteria. Broad spectrum activity will allow for targeting of pathogens with
different structures and cell membrane components.
This work focuses on the synthesis of a dual antibiotic agent, composed of a cationic
amphiphilic polyproline helix (CAPH) possessing cell penetrating and nonmembrane lytic
antimicrobial capabilities (P14LRR), and a derivative of the polymyxin B (PMX) antibacterial
peptide. This dual antibiotic conjugate was created to be a tool to potentially clear intracellular
pathogenic bacteria. Overall, the reduction of the disulfide bond linking the two antibiotics within
the reducing environment of cells would release the individual antimicrobial agents, and could
have improved cell membrane penetration and intracellular synergistic activity. Herein, the
synthesis of the dual antibiotic agent, P14LRR-PMX, is discussed.
History
Degree Type
- Master of Science
Department
- Chemistry
Campus location
- West Lafayette
