Date Approved

9-22-2020

Embargo Period

9-22-2020

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Caputo, Gregory A.

Committee Member 1

Vaden, Timothy D.

Committee Member 2

Perez, Lark J.

Keywords

microbials, antimicrobial resistance, antimicrobial peptides, ionic liquids, ponericin L1

Subject(s)

Peptide antibiotics

Disciplines

Medicinal and Pharmaceutical Chemistry

Abstract

Non-traditional antimicrobials have been an area of great interest due to the increasing prevalence of antimicrobial resistance (AMR) in bacteria. Antimicrobial peptides (AMPs) & ionic liquids (ILs) are two examples that have been investigated as a potential solution. Most AMPs are naturally derived & exhibit high selectivity against bacterial targets over host cells. The venom-derived peptide, ponericin L1 from Neoponera goeldii, was used to investigate the role of cationic residues & net charge on peptide activity. Using both in vitro & microbiological methods, L1 peptide & derivatives exhibited an alpha-helical conformation with enhanced binding to lipid vesicles containing anionic lipids & low hemolytic activity. Net charge & identity of the cationic groups on the peptide were shown to play a significant role in antimicrobial activity. ILs have also been investigated in combination with antimicrobial compounds to fight AMR. Imidazolium chloride-based ILs with differing alkyl tails & commercially available antibiotics were used to examine the potential for synergistic effects on multiple bacteria. Analysis of the IL data indicates that length of the alkyl chain plays a crucial role in antimicrobial activity & cytotoxicity. A synergistic effect was exhibited while showing low cytotoxicity when tested in a mammalian cell culture model.

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