Issue 43, 2022

Tyrosine bioconjugation with hypervalent iodine


Hypervalent iodine reagents have recently emerged as powerful tools for late-stage peptide and protein functionalization. Herein we report a tyrosine bioconjugation methodology for the introduction of hypervalent iodine onto biomolecules under physiological conditions. Tyrosine residues were engaged in a selective addition onto the alkynyl bond of ethynylbenziodoxolones (EBX), resulting in stable vinylbenziodoxolones (VBX) bioconjugates. The methodology was successfully applied to peptides and proteins and tolerated all other nucleophilic residues, with the exception of cysteine. The generated VBX were further functionalized by palladium-catalyzed cross-coupling and azide–alkyne cycloaddition reactions. The method could be successfully used to modify bioactive natural products and native streptavidin to enable thiol-mediated cellular uptake.

Graphical abstract: Tyrosine bioconjugation with hypervalent iodine

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Article information

Article type
Edge Article
15 Aug 2022
03 Oct 2022
First published
12 Oct 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, 12808-12817

Tyrosine bioconjugation with hypervalent iodine

N. Declas, J. R. J. Maynard, L. Menin, N. Gasilova, S. Götze, J. L. Sprague, P. Stallforth, S. Matile and J. Waser, Chem. Sci., 2022, 13, 12808 DOI: 10.1039/D2SC04558C

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