Issue 9, 2022

A novel tyrosine hyperoxidation enables selective peptide cleavage

Abstract

A novel tyrosine hyperoxidation enabling selective peptide cleavage is reported. The scission of the N-terminal amide bond of tyrosine was achieved with Dess–Martin periodinane under mild conditions, generating a C-terminal peptide fragment bearing the unprecedented hyperoxidized tyrosine motif, 4,5,6,7-tetraoxo-1H-indole-2-carboxamide, along with an intact N-terminal peptide fragment. This reaction proceeds with high site-selectivity for tyrosine and exhibits broad substrate scope for various peptides, including those containing post-translational modifications. More importantly, this oxidative cleavage was successfully applied to enable sequencing of three naturally occurring cyclic peptides, including one depsipeptide and one lipopeptide. The linearized peptides generated from the cleavage reaction significantly simplify cyclic peptide sequencing by MS/MS, thus providing a robust tool to facilitate rapid sequence determination of diverse cyclic peptides containing tyrosine. Furthermore, the highly electrophilic nature of the hyperoxidized tyrosine unit disclosed in this work renders it an important electrophilic target for the selective bioconjugation or synthetic manipulation of peptides containing this unit.

Graphical abstract: A novel tyrosine hyperoxidation enables selective peptide cleavage

Supplementary files

Article information

Article type
Edge Article
Submitted
09 Nov 2021
Accepted
10 Feb 2022
First published
11 Feb 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 2753-2763

A novel tyrosine hyperoxidation enables selective peptide cleavage

S. Zhang, L. M. De Leon Rodriguez, F. F. Li, R. Huang, I. K. H. Leung, P. W. R. Harris and M. A. Brimble, Chem. Sci., 2022, 13, 2753 DOI: 10.1039/D1SC06216F

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