Issue 1, 2014

Chemoselective sulfenylation and peptide ligation at tryptophan

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.

Graphical abstract: Chemoselective sulfenylation and peptide ligation at tryptophan

Supplementary files

Article information

Article type
Edge Article
Submitted
28 May 2013
Accepted
09 Oct 2013
First published
10 Oct 2013

Chem. Sci., 2014,5, 260-266

Chemoselective sulfenylation and peptide ligation at tryptophan

L. R. Malins, K. M. Cergol and R. J. Payne, Chem. Sci., 2014, 5, 260 DOI: 10.1039/C3SC51497H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements