Electronic Theses and Dissertations

Date of Award

5-1-2026

Document Type

Thesis

Degree Name

M.S. in Chemistry

First Advisor

Jinchao Lou

Second Advisor

Daniell Mattern

Third Advisor

Saumen Chakraborty

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

Developing chemical tools to investigate the assembly and biosynthesis of peptides and biomolecules is crucial for deeper understanding of underlying biological mechanisms, allowing for the advancement of therapeutic strategies and systems. The first part of the thesis focuses on tools to modulate pathological peptide assemblies, such as amyloid beta (A?). Alzheimer’s disease (AD) is the most common form of dementia, with an increasing number of cases each year. Misfolding and aggregation of amyloid beta (A?) peptides are a hallmark of AD, which is characterized by progressive memory loss, behavioral changes, and cognitive impairment. Although treatments are available, they primarily offer symptomatic relief in early or moderate stages of AD progression. A growing area of interest in the field of biomedicine is ionic liquids (ILs) which have highly tunable properties, making them highly versatile. Previous work has demonstrated that ILs can dissolve insulin amyloid aggregates, suggesting that this strategy can be extended to A? aggregates, providing a potential alternative treatment for AD. In this thesis, six biocompatible ionic liquids (CAOA, CA2OE, CA3OE, CANA, CA2NE, CA3NE) were evaluated for their ability to disrupt fibrillar A? aggregates. Additionally, the minimum IL-to-monomer concentration ratio for inhibiting A? monomer-to-fibril aggregation was determined for the best-performing IL. The results revealed that CA3OE was the best-performing IL with a minimum IL-to-monomer concentration ratio of 150x. CA3OE shows potential in the development of alternative treatments for AD.

In a separate effort, we developed tools to track biomolecule synthesis, such as PG. Peptidoglycan (PG) is an essential component of bacterial cell walls, providing structural integrity and protection against external pressure. Since PG plays a key role in bacterial survival, it can be targeted by antibiotics to either kill the bacteria or inhibit their growth. Understanding the biosynthetic pathway of PG is critical for the development of drugs that effectively target PG. Metabolic labeling using D-amino acid probes can be utilized to investigate PG, offering insight into formation, growth, and morphology. In this thesis, a D-amino acid derivative control probe was successfully synthesized, providing the first step toward effective PG labeling and enzyme integration.

Available for download on Wednesday, August 02, 2028

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