Date of Graduation

Summer 8-31-2024

Document Type

Thesis

Degree Name

Master of Science in Chemistry

College/School

College of Arts and Sciences

Department/Program

Chemistry

First Advisor

Michael Stevenson, PhD

Second Advisor

Janet Yang, PhD

Third Advisor

Natalia Powers-Riggs, PhD

Abstract

The rate of antimicrobial-resistant infections has increased exponentially since the emergence of the first antibiotic, leading to a global public health threat as current treatments become less effective against such infections. The search for novel treatment options has led to the investigation of antimicrobial peptides (AMPs), which possess broad-spectrum activity against pathogens. These small, naturally-occurring peptides are involved in the innate immune responses of a diverse range of species. A handful of these AMPs bind to metal ions such as Cu(II) and Zn(II), and the metal-peptide complex often demonstrates increased antimicrobial activity which remains to be understood. The sequence of some Cu(II)-binding AMPs contain a well-conserved motif called the amino terminal copper and nickel (ATCUN) binding motif which consists of the following amino acids: H2N-X1-X1-His3. In contrast, Zn(II) binding does not occur in coordination with motifs as well-conserved but, rather, with histidine-rich sequences of which the imidazole nitrogens and other residue side chains coordinate with the metal ion. In this study, we examine the metal-binding properties of Holothuroidin-2 (H2), an AMP originating from the tubular sea cucumber with antibiofilm properties. This 14-residue-long peptide contains the ATCUN motif and four histidine residues which have yet to be investigated for metal interactions. This study quantifies the binding thermodynamic properties between H2 and Cu(II) and Zn(II) using isothermal titration calorimetry (ITC) and the metal-induced structural changes with nuclear magnetic resonance (NMR) spectroscopy.

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Available for download on Wednesday, August 30, 2034

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