In Vitro Selection of mRNA-Display Libraries Containing Unnatural Amino Acids

Author: Li, Shuwei

Year: 2003

Degree: Dissertation (Ph.D.)

Advisor: Roberts, Richard W.

Committee Members: Dervan, Peter B.; Bercaw, John E.; Roberts, Richard W.; Mayo, Stephen L.

Option: Chemistry

DOI: 10.7907/NVCQ-JS95

Abstract

The mRNA display library provides a strategy to make up to 1013 unique peptides that fuse with their own genes via a covalent link. In this thesis, several strategies to prepare mRNA display libraries containing unnatural side chains are described. Chapter 1 is a short introduction and application of mRNA-display technology. Chapter 2 describes a chemical derivatization strategy to append an unnatural side chain to libraries. Chapter 2 introduces the incorporation of unnatural amino acids via non-sense codon suppression. Chapter 4 focuses on the catalytic selection with mRNA display libraries. These libraries should facilitate the discovery of novel ligands with functionalities beyond those provided by the 20 naturally occurring amino acids.

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