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Phage-Based Bioimaging Agents and a Selection Technique for the Directed Evolution of Proteases

Abstract

This dissertation is divided into two research areas: phage-based bioimaging agents, and selection techniques for the directed evolution of proteases. Chapter one describes the nanoparticle properties that affect biodistribution and gives examples of phage-based imaging agents. Chapter two begins with a summary of bacteriophage MS2 properties and goes on to describe how this icosahedral virus has been functionalized to create imaging agents. Chapter two also highlights improvements in chemoselective coupling chemistries that were discovered in the process of functionalizing bacteriophage MS2. Chapter three describes methodology for the N-terminal labeling of filamentous phage. This technology is applied to create cancer cell imaging agents. Chapter 4 describes a different research area, explaining a selection technique for the directed evolution of proteases. This selection is used to identify a tobacco etch virus (TEV) protease mutant with altered sequence specificity.

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