Tyrosine bioconjugation with hypervalent iodine (original) (raw)

Author affiliations

* Corresponding authors

a Laboratory of Catalysis and Organic Synthesis, Institut des Sciences et Ingénierie Chimique, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
E-mail: jerome.waser@epfl.ch

b Department of Organic Chemistry, University of Geneva, 1211 Geneva, Switzerland
E-mail: stefan.matile@unige.ch

c Institut des Sciences et Ingénierie Chimique, Ecole Polytechnique Fédérale de Lausanne, EPFL, 1015 Lausanne, Switzerland

d Department of Paleobiotechnology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), 07745 Jena, Germany

e Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), 07745 Jena, Germany

Abstract

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

DOI

https://doi.org/10.1039/D2SC04558C

Article type

Edge Article

Submitted

15 Aug 2022

Accepted

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

Download Citation

Chem. Sci., 2022,13, 12808-12817

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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, 12808DOI: 10.1039/D2SC04558C

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