.beta.-sheet mimetics and methods relating to the same are disclosed. The .beta.-sheet mimetics have utility as protease and kinase inhibitors, as well as inhibitors of transcription factors and protein-protein binding interactions. Methods of the invention include administration of a .beta.-sheet mimetic, or use of the same for the manufacture of a medicament for treatment of a variety of conditions associated with the targeted protease, kinase, transcription factor and/or protein-protein binding interaction.