| The focus of this thesis is the design of biologically active beta-peptides and the effects of substituting non-natural analogues of the amino acid arginine into alpha-peptides. Naturally-occuring alpha-peptides and non-natural beta-peptides are just two examples of numerous compounds classified as foldamers. These are ideal for studies since both are synthetically accessible and adopt well-defined structures. Studies involving beta-peptides were undertaken with the purpose of creating peptidomimetics that could participate in protein-protein interactions based on natural models. Studies with alpha-peptides substituted with arginine analogues served to explore the importance of sidechain length in peptide stability and biological activity, thus providing insight into nature's selection of arginine as one of the 20 naturally-occurring amino acids. Foldamer design can be classified in 4 separate ways (discussed later) - direct sequence conversion, distribution of physicochemical properties, modular assembly, and grafting bioactive functionality. Each of the projects presented in this thesis utilized one of these design strategies for obtaining the appropriate alpha- or beta-peptides. These design strategies have been employed numerous times for studying several different classes of foldamer scaffolds, therefore providing context for the results presented in this thesis. |
