AMR Completed Master's Thesis 2021.pdf (1.5 MB)

Synthesis of a Cationic Amphiphilic Polyproline Helix (CAPH) Conjugate with Polymyxin B

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posted on 23.07.2021, 16:41 by Ambar M RosarioAmbar M Rosario
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

Advisor/Supervisor/Committee Chair

Jean Chmielewski

Additional Committee Member 2

Angeline Lyon

Additional Committee Member 3

Herman Sintim

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