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

First Advisor

Caputo, Gregory A.

Second Advisor

Vaden, Timothy D.

Third Advisor

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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