Expanding Chemical and Structural Space in mRNA Display

Abstract

In vitro translation provides a useful toolbox for the chemical biologist because of its multiple applications, such as protein/peptide synthesis, protein folding studies and rapid identification of genes. By reprogramming the genetic code within this system we can incorporate nonstandard amino acids to further expand the applications, such as site-specific labelling of proteins, mRNA display with an expanded chemical space and to provide handles for biorthogonal reactions on proteins/peptides. This thesis outlines the steps involved in bacterial translation, how this can be used to pan libraries of peptides at ultra-high numerical diversity, how genetic code expansion can be used to extend the chemical diversity within these, and some of the opportunities for even further modification provided by bio-orthogonal reactions.