Date of Graduation

Summer 8-31-2023

Document Type

Thesis

Degree Name

Master of Science in Chemistry

College/School

College of Arts and Sciences

Department/Program

Chemistry

First Advisor

Michael Stevenson

Abstract

There is an emerging crisis in healthcare from a rise in antibiotic resistance coupled with a decrease in novel antibiotic development which is making it more difficult to treat individuals with infections. An attractive alternative for novel therapies is antimicrobial peptides (AMPs) which are naturally occurring peptides in the innate immune response and found in many forms of life. They are produced to protect the host from pathogens like gram-negative and gram-positive bacteria and fungi, and some even have antiviral and anticancer activity. Because of their broad-spectrum activity and low rates ofpathogen resistance, antimicrobial peptides are an attractive alternative to traditional antibiotics. Interestingly, some AMPs are activated by metal ions such as Zn(II) and Cu(II), and confer two major modes of action like nutritional immunity and the formation of reactive oxygen species. Indeed, one such AMP is PG-KI (Pseudophryne güntheriKassinin-1). It is an 11-residue (EPHPDEFVGLM) peptide found in the Austrailian frog, which has a motif that resembles an Amino Terminal Cu(II) and Ni(II) (ATCUN) binding motif. In PG-KI a proline exists in the first two residues making it a pseudo-ATCUN motif. Moreover, PG-KI and some peptide families, including various neuropeptides, contain a posttranslational modification (PTM) at the N-terminus resulting in intramolecular cyclization of a terminal glutamate or glutamine to form pyroglutamate (pGlu). This work quantifies the Cu(II)-binding thermodynamics imparted on three variants of PG-KI to probe the effect of proline and this PTM. The insight learned from PG-KI may be applied to and help understand other peptides with similar sequences.

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Available for download on Thursday, August 27, 2026

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