Date of Award

2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Amos B. Smith, III

Abstract

ABSTRACT

EXPANDING PEPTIDE STAPLING WITH s-TETRAZINE

Matthew H. Bunner

Professor Amos B. Smith, III

This dissertation presents efforts toward the extension of synthetic methods for the creation of peptide macrocycles via the addition of dichloro-s-tetrazine to peptide sequences containing lysine, serine, threonine, and tyrosine. Chapter one reviews the work and interest of the Smith group in the s-tetrazine chromophore and the history of stapled peptides in the chemical literature. Chapter two describes (A) the development of a synthetic protocol for the creation of peptide macrocycles from peptide sequences containing a single cysteine and a single lysine residue using dichloro-s-tetrazine including discussion on amino acid tolerance and seven successful examples, (B) efforts toward the development of a synthetic protocol for the creation of peptide macrocycles from peptide sequences containing a single cysteine residue and a single serine / threonine / tyrosine residue, and (C) efforts toward the investigation of the photochemical dissociation of the created cysteine / lysine peptide macrocycles. Chapter three describes our efforts to improve the synthesis of dichloro-s-tetrazine in a large-scale procedure.

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