The synthesis and application of conformationally restricted cystine and proline mimetics

Chemical modifications to peptide sequences can provide improved sequence stability, in vivo potency and inform the design of small molecule mimetics of peptide structure. This thesis addressed synthetic routes for disulfide replacement and focused on the installation of the alkyne motif, making it compatible with modern click chemistry. The backbone flexibility of peptides was also explored through modification of the heterocyclic residue proline and a pseudoproline library was developed for controlling conformational dynamics. This work culminated in the design and synthesis of a potent analgesic conotoxin sequence providing an important connection between structure and activity.