Date of Award

12-4-2023

Document Type

Thesis

Degree Name

Bachelor of Science

Department

Biochemistry & Molecular Biol.

First Advisor

Christopher Shugrue

Abstract

Within the field of medicine and pharmacology, discovering small molecule or biologic based molecules with therapeutic potential is a difficult task. Current methods involve individually screening hundreds of compounds on a potential target biomolecule, and recent technologies have explored peptide encoded libraries (PELs) as a means of making this screening process more high-throughput. These libraries produce a large number of small molecule drug candidates each conjugated to a unique peptide fragment, functioning as a barcode. Analysis of PELs requires the capture of hit small molecules and the subsequent release of their peptide tags; however, current approaches are limited in their ability to efficiently release these peptides. My work explores the use of a diaryl oxazole as a cleavable linker that is released in mild oxidative conditions to gently liberate peptide labels from captured hits. Oxazoles are an encouraging class of cleavable linkers for peptide-based research due to their ability to be modified with functional groups necessary for solid-phase peptide synthesis, as well as their stability to the harsh conditions associated with this process. The developed cleavable linker also demonstrates compatibility with a variety of natural and abiotic amino acids. Peptide-embedded diaryl oxazoles are quantitatively cleaved in 15 minutes through single-electron oxidation with cerium (IV) ammonium nitrate under mild conditions at ambient temperature. Our reported diaryl oxazole-based linker shows promise as a novel mechanism for the mild release of peptide labels in PELs. Oxazoles as cleavable linkers provide further opportunity for screening methods in the drug discovery pathway.

Additional Files
2023-Taggart-form.pdf (578 kB)
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