Chemoselective sulfenylation and peptide ligation at tryptophan

Lara R. Malins, Katie M. Cergol, Richard J. Payne*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Peptide ligation-desulfurization chemistry at 2-thiol tryptophan (Trp) is described for the first time. Installation of a thiol auxiliary was achieved through late-stage chemoselective sulfenylation chemistry at the 2-position of the indole ring of Trp either in solution or on solid support, thus abrogating the need for the preparation of a pre-formed thiolated amino acid. Peptides possessing the 2-thiol Trp functionality on the N-terminus were shown to facilitate high yielding ligation reactions with a variety of C-terminal peptide thiophenyl thioesters. Efficient removal of the 2-thiol Trp auxiliary following the ligation reactions was achieved via reductive desulfurization and provided native peptide products in excellent yields. The utility of the methodology was demonstrated in the synthesis of a glycosylated fragment of the N-terminal extracellular domain of the chemokine receptor CXCR1.

Original languageEnglish
Pages (from-to)260-266
Number of pages7
JournalChemical Science
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 2014
Externally publishedYes

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