Document Type

Honors Project On-Campus Access Only

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Advisor: Leah Witus

Abstract

Peptidomimetics can expand natural peptide diversity by incorporating unnatural structures. We have developed a pre-monomer synthetic route towards peptidomimetics, where backbone elongation and side chain addition are separated into independent steps. This allows facile incorporation of unnatural side chains during solid phase synthesis without synthesizing individual protected monomers. This has been achieved using the thiol-ene click-coupling reaction wherein a thiol-containing side chain is attached to an alkene reactive handle on the pre-monomer backbone. We have optimized the thiol-ene reaction conditions to achieve high coupling efficiencies on the solid phase and applied these conditions towards the synthesis of pentamer-length thioether-linked peptidomimetics.

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