Date of Award


Degree Name

Doctor of Philosophy




Katja Michael


We describe the development of a novel resin with a photoreactive N-acylnitroindoline linker that allows for the synthesis of amino acid- (in solution) or peptide-α-thioesters using standard Fmoc/t-Bu standard solid phase peptide synthesis (SPPS). Recent advances have shown that the yields of this thioesterification reaction have dramatically increased due to a simple change in the order of addition of reagents. Upon illumination with UV-light, in the presence of N-hydroxybenzotriazole (HOBt), the amino acid- or peptide-α-OBt ester is generated by direct photo-release from the nitroindoline linker with minimal epimerization, followed by reaction with thiophenol in the dark to produce amino acid-α-phenylthioesters or peptide-α-phenylthioesters. Nine amino acid-α-phenylthioesters of the twenty proteinogenic amino acids were prepared in high yield and high purity. Eight photoreactive tripeptides were prepared on Rink Amide resin following Fmoc-based SPPS strategies and cleaved to give their corresponding photoreactive tripeptide amides. Seven tripepide-α-phenylthioesters were prepared in high yield and high purity. Three tripeptide-α-phenylthioesters were prepared in good yield by direct photo-release from the solid support. Five photoreactive glycopeptides based on sequences found in human erythropoietin and the GP-120 HIV-1 envelope protein were synthesized and cleaved from Rink Amide resin for future conversion to their corresponding thioesters.




Received from ProQuest

File Size

148 pages

File Format


Rights Holder

Tyrone Hogenauer