Author ORCID Identifier

https://orcid.org/0000-0002-5825-1203

Defense Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Matthew C.T. Hartman

Second Advisor

T. Asthon Cropp

Third Advisor

Scott Gronert

Fourth Advisor

Soma Dhakal

Fifth Advisor

Christopher Lemmon

Abstract

The ability of incorporation non-canonical amino acids (ncAAs) using translation offers researchers the ability of extend the functionality of proteins and peptides for many applications including synthetic biology, biophysical and structural studies, and discovery of novel ligands. Here we describe the three projects where the addition of ncAAs to in vitro translation systems creates useful chemical biology techniques. In the first, a fluorinated histidine derivative is used to create a novel affinity tag that allows for the selective purification of peptides from a complex mixture of proteins. In the second, the high promiscuity of an editing-deficient valine-tRNA synthetase (ValRS T222P) is used to demonstrate ribosomal translation of 13 ncAAs including those with novel side chains, α,α disubstitutions, and cyclic β amino acids. Lastly, a couple of these amino acids are integrated into the powerful ligand discovery tool of mRNA display for the discovery of helical peptide ligands.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-10-2018

Available for download on Saturday, August 05, 2023

Share

COinS