Chemistry Commons^™

The Development Of Intrinsically Cell-Permeable Peptide Libraries Using Mrna Display, Nicolas A. Abrigo

Theses and Dissertations

Peptides are emerging as promising therapeutics due to their inhibitory affinity towards protein-protein interactions (PPI). However, peptides have been limited mainly by their poor bio-stability and lack of cell permeability. Efforts to generate drug-like peptides have led to the development of macrocyclic peptides, which exhibit improved stability. Yet, most macrocyclic peptides still require the assistance of a cell penetrating peptide (CPP) for cellular entry.

High throughput technologies have been exceptional tools for the discovery of peptides to interrupt PPIs. This work details the recent advancements we have made to improve our high throughput technique, mRNA display, to yield more therapeutically …

The Development Of Bicyclic Peptide Library Scaffolds And The Discovery Of Biostable Ligands Using Mrna Display, David E. Hacker

Theses and Dissertations

Peptides are a promising class of therapeutic candidates due to their high specificity and affinity for cellular protein targets. However, peptides are susceptible to protease degradation and are typically not cell-permeable. In efforts to design more effective peptide drug discovery systems, investigators have discovered that incorporation of non-canonical amino acids (ncAAs) and macrocyclization overcome these limitations, making peptides more drug-like.

In this work, we exploit the promiscuity of wild-type aminoacyl-tRNA synthetases (aaRSs) to ‘mischarge’ ncAAs onto tRNA and ribosomally incorporate them into peptides using a cell-free translation system. We have demonstrated the ability to incorporate five ncAAs into a single …

Investigations Into The Fluorescent Covalent Labeling Of Biomolecules Utilizing Rhodamine Dyes, Electrophilic Leaving Groups And Mrna Display., Susan D. Selaya

Theses and Dissertations

The discovery of a method by which proteins of interest can selectively be labeled with a probe of choice intracellularly is a longstanding goal in chemical biology research. Conventional labeling techniques have utilized large domain tags but despite the development of small labeling molecules there have been no short peptide sequences known to covalently label a small molecule without the aid of an enzymatic process or metal chelation. We aimed to find a sequence of nucleophilic peptides that reacted covalently and specifically with electrophilic small labeling molecules using mRNA display. Our goal was to show that an electrophilic small labeling …