Date of Award
Doctor of Philosophy (PhD)
Mark L. McLaughlin
Several different peptides exhibit antimicrobial activity based upon an amphiphilic $\alpha$-helical secondary structure. Antimicrobial action occurs because these peptides compromise the integrity of the cell membrane and ultimately cause cell lysis. It is believed that ion-channel formation is the mechanism by which this lysis occurs. The goal of this research has been to conduct structure-function studies of synthetic peptides to aid in the determination of the mode of action of lytic peptides. Several peptides based upon a minimalist approach have been synthesized. Amphiphilicity and $\alpha$-helicity were the desired structural features. With these as the necessary structural motifs we set out to prepare peptides with very simple primary structures. This has been accomplished in the form of peptides based upon a heptad repeat. By altering one residue of the repeat unit, changes can be made in the secondary structure very easily. Also, the simplicity of the design allows for facile large scale preparation using solution-phase synthesis. The design, synthesis, biological activity, and secondary structural determination are discussed. Also, improved syntheses of benz(f) indene and dibenzfluorenone are recounted. These compounds have been prepared for the synthesis of benz-annulated indenyl metal complexes in order to explore the reactivity of these unknown complexes. These complexes may exhibit anthracene like character and undergo Diels-Alder reactions or photochemical couplings at the middle rings of the complex. The benz (f) indene ligand was prepared by two different routes and the dibenzfluorenone by one all of which were improvements over the published literature syntheses.
Becker, Calvin Lawrence, "The Design, Synthesis and Structure-Function Studies of Highly Repetitive Amphiphilic Antibacterial Peptides and the Synthesis of Benz(f)indene for the Preparation of Novel Metallocenes." (1994). LSU Historical Dissertations and Theses. 5709.