Date of Award

1996

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Mark McLaughlin

Abstract

Peptides exhibit properties based on the amino acids present in the peptide and structure the peptide assumes in its environment. For example, peptides have been shown to be antimicrobial when they are amphipathic and in an $\alpha$-helical shape. The mechanism for this antimicrobial activity is subject to dispute. One theory states that the peptides work by forming a "pore" through the cell membrane which causes a depolarization of the membrane and the cell lysis because of osmosis. Another theory states that the peptides merely compromise the integrity of the membrane by solubilizing the membrane. In order for the "pore" theory of lytic activity to occur, the peptides must arrange themselves in a discrete aggregated fashion. The goal of this research is to explore the nature of the aggregated state of designed peptides through the use of CD spectroscopy and fluorescent labeling. Several peptides were designed using a minimalist approach and were measured using CD spectroscopy to explore how the placement of leucines in the peptides cause a change in their propensity for aggregation. Using this information, the site for an incorporation of a fluorescently labeled peptide was chosen. The synthesis of the fluorescently labeled amino acid presented an opportunity to explore different types of glycine templates and to find a quicker method for making the amino acid in high yields. After the synthesis of the amino acid, it was incorporated into the peptides and CD and fluorescence studies were accomplished. The result shows the peptides, when aggregated, align themselves in an antiparallel fashion.

ISBN

9780591289039

Pages

74

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