Issue 47, 2022

Direct formation and site-selective elaboration of methionine sulfoximine in polypeptides

Abstract

Sulfoximines are emerging moieties for medicinal and biological chemistry, due in part to their efficacy in selective inhibition of amide-forming enzymes such as γ-glutamylcysteine synthetase. While small-molecule sulfoximines such as methionine sulfoximine (MSO) and its derivatives are well studied, structures with methionine sulfoximine residues within complex polypeptides have been generally inaccessible. This paper describes a straightforward means of late-stage one-step oxidation of methionine residues within polypeptides to afford NH-sulfoximines. We also present chemoselective subsequent elaboration, most notably by copper(II)-mediated N–H cross-coupling at methionine sulfoximine residues with arylboronic acid reagents. This development serves as a strategy to incorporate diverse sulfoximine structures within natural polypeptides, and also identifies the methionine sulfoximine residue as a new site for bioorthogonal, chemoselective bioconjugation.

Graphical abstract: Direct formation and site-selective elaboration of methionine sulfoximine in polypeptides

Supplementary files

Article information

Article type
Edge Article
Submitted
28 Jul 2022
Accepted
13 Nov 2022
First published
14 Nov 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 license

Chem. Sci., 2022,13, 14101-14105

Direct formation and site-selective elaboration of methionine sulfoximine in polypeptides

Y. Ding, S. S. Pedersen, A. Lin, R. Qian and Z. T. Ball, Chem. Sci., 2022, 13, 14101 DOI: 10.1039/D2SC04220G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements