Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry, Organic

Date of Defense

8-12-2016

Graduate Advisor

George Gokel, Ph.D.

Committee

James K. Bashkin

Michael R. Nichols

Christopher D. Spilling

Abstract

Amphiphiles are molecules that contain both water-soluble and water-insoluble components. The dual nature of these molecules engenders remarkable properties including the ability to self-assemble into ordered structures. Cell membranes are composed of amphiphilic phospholipids that organize into a bilayer motif. Synthetic amphiphiles can interact with natural membranes and influence the transport of molecules across the cell membrane. The work elaborated in this report employs amphiphiles to co-assemble with DNA and transport the genetic material across cell membranes. First, a simplified method for interacting DNA with amphiphiles was developed. Second, a series of known ion-transporting compounds were assayed for their interaction with DNA. Finally, a new class of DNA-binding molecules was designed and characterized. The findings have application in biological research and potentially in gene therapy to cure disease. In addition, some of the molecules designed in this study were found to have antimicrobial properties. These compounds were shown to reverse antimicrobial resistance when co-administered with another antibiotic. Mechanistic studies suggest that the compounds are membrane-active, which implies a more general strategy for combating antibiotic resistance. Together, this work represents a structure-based approach to the understanding of how amphiphilic small molecules interact within biologically relevant systems.

Included in

Chemistry Commons

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