Synthesis of peptide-alpha-phenylthioesters using a solid support with a photoreactive nitroindoline moiety

Andrew Pardo, University of Texas at El Paso

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.^

Subject Area

Chemistry, Organic

Recommended Citation

Pardo, Andrew, "Synthesis of peptide-alpha-phenylthioesters using a solid support with a photoreactive nitroindoline moiety" (2014). ETD Collection for University of Texas, El Paso. AAI3636294.
http://digitalcommons.utep.edu/dissertations/AAI3636294

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