Author

Evan Wolff

Date of Award

2024

Document Type

Thesis

Degree Name

Bachelor of Science

Department

Biochemistry & Molecular Biol.

First Advisor

Dr. Christopher Shugrue

Second Advisor

Dr. Jonathan Dattelbaum

Abstract

The development of new cleavable linkers increases the diversity of compatible conditions for peptide discovery platforms. Potential applications for these linkers include high-throughput pharmaceutical candidate screening when utilized in Peptide Encoded Libraries (PELs). This thesis describes the development of a bifunctional diaryl oxazole-based cleavable linker that may be incorporated into compounds through Solid-Phase Peptide Synthesis (SPPS). This oxazole-based linker may be rapidly cleaved by cerium ammonium nitrate in aqueous conditions and is compatible with most natural amino acids and a variety of unnatural amino acids. This linker represents the first single-electron oxidant labile linker described to our knowledge and it demonstrates orthogonal cleavage to traditional oxidatively cleaved linkers. A greater diversity of cleavable linkers increases the versatility of various peptide discovery platforms and oxazole-based linkers demonstrate novel mechanisms for the mild oxidative release of attached compounds.

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