Date of Award
Bachelor of Science
Biochemistry & Molecular Biol.
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.
Taggart, Elizabeth, "Diaryl Oxazoles as Cleavable Linkers for Drug Discovery Platforms" (2023). Honors Theses. 1732.