One of the most exciting frontiers of expanding pharmacopeia to combat currently untreatable diseases is achieving specifically and potently disruption of unwanted protein-protein interactions where traditional small molecule drugs tend to fall short. Our laboratory has developed the methodology of peptide stapling and pioneered successful applications in multiple disease models since its induction over a decade ago. One common feature of past applications is the use of a single stapled peptide in helical form, derived from the natural binding interface of target proteins. This dissertation ventures into protein interactions that involve multiple components and sites and explores the extended use of stapled peptides in these volatile settings.
