Date of Award

2014-01-01

Degree Name

Doctor of Philosophy

Department

Chemistry

Advisor(s)

Katja Michael

Abstract

Peptide-alpha-phenylthioesters are particularly reactive starting materials for Native Chemical Ligation. Here we present a new photochemical method for the synThesis of peptide-alpha-phenylthioesters under neutral reaction conditions with various C-terminal amino acids. The peptides were synthesized by Fmoc strategy on Sieber amide resin with a photoreactive nitroindoline linker. After cleavage of the photoreactive and fully protected peptide from the beads with dilute trifluoroacetic acid an auxiliary nucleophile such as N-hydroxybenzotriazole or N-hydroxysuccinimide is used to photochemically generate the activated peptide ester in situ. Then thiophenol is introduced in the dark. This new method enabled us to synthesize peptide-alpha-phenylthioesters up to 21 amino acids long in good to high yields, and with low levels of epimerization at the C-terminal.

Language

en

Provenance

Received from ProQuest

File Size

191 pages

File Format

application/pdf

Rights Holder

Andrew Pardo

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