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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

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

Ambar M Rosario (11014752) 23 July 2021 (has links)
Pathogens such as <i>Listeria</i>, <i>Shigella</i>, <i>Brucella</i>, <i>Salmonella</i>, <i>Mycobacterium tuberculosis</i> and <i>methicillin-resistant Staphylococcus aureus</i> (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.<div>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. </div>

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