Ketone-derived Diazo-iodonium Salts as Reagents for Methionine-selective Functionalization

Zhang-He Goh; Matthew J. Gaunt

doi:10.1055/a-2760-7405

Synlett, Table of Contents

Synlett
DOI: 10.1055/a-2760-7405

Letter

Ketone-derived Diazo-iodonium Salts as Reagents for Methionine-selective Functionalization

Authors

Zhang-He Goh

¹Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
Matthew J. Gaunt

¹Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)

Abstract

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Dedication

This paper is dedicated to Professor Steven V. Ley on occasion of his 80th birthday.

Abstract

Selective modification of methionine residues provides a valuable strategy for the site-specific labeling of proteins and peptides. We describe here the synthesis and evaluation of aryl ketone-derived diazo hypervalent iodine reagents as tools for this transformation. These reagents display enhanced reactivity compared to their ester counterparts, enabling efficient modification across a selection of peptide and small protein systems. This was particularly prominent in cases where the methionine residue is buried, such as in ubiquitin, where significant differences in performance were observed between the ketone- and ester-derived reagents. The aryl ketone scaffold allows straightforward incorporation of bioorthogonal handles, facilitating downstream functionalization. These findings broaden the scope of our methionine-directed bioconjugation and highlight opportunities for the development of new chemical biology applications.

Keywords

Methionine - Bioconjugation - Iodonium salt - Diazo - Protein

Full Text

References

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