Graduation Year

2021

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Chemistry

Major Professor

James Leahy, Ph.D.

Committee Member

Theresa Evans-Nguyen, Ph.D.

Committee Member

Jianfeng Cai, Ph.D.

Committee Member

Michael White, Ph.D.

Keywords

FKBP12, Shield-1, toxoplasmosis, destabilizing domain, avibactam, β-lactamase inhibitors, Pseudomonas aeruginosa, Clostridioides difficile

Abstract

Drug discovery’s impact on modern healthcare cannot be measured. In the past year, the world has watched scientists all around the globe work together to help protect the public from the novel coronavirus pandemic. Although sometimes slow and costly, drug discovery is important for advancing modern society. Drug discovery is at the core of treating diseases and in particular, infectious diseases. In the first chapter an overview of drug discovery will be discussed in a brief manner.

The second chapter will introduce infectious diseases. In modern society, the development of small molecule treatments for treating bacteria, viruses, and fungi has been quintessential in the survival of our species. Infectious diseases are spread across the globe and commonly affect less developed areas as a death sentence. Some infectious diseases such as Toxoplasma gondii are prevalent all around the world even in the modern era. Although less deadly than many pathogens, T. gondii is a protozoan parasite that causes a lasting infection. The third chapter will discuss probing the molecular pathways of T. gondii through the use of small synthetic molecules.

Treatments for bacterial infections have just been discovered within the past century. Penicillin and sulfa drugs had an immense impact on the fight against bacterial infections. It was just in the early 1900s that bacterial infections were a leading cause of death in the United States. Still, society must remain vigilant against these infections. Multi-drug resistant bacteria are becoming a terrifying reality where we are unable to treat some bacterial infections with even the strongest antibiotics developed by humans. New treatments for bacterial infections are necessary for the advancement of medicine because so many of our current standards of care are quickly becoming obsolete to ever evolving bacterial strains. The fourth and last chapter will discuss combatting antibiotic resistance recycling previous scaffolds used in the area.

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