Tyrosine bioconjugation with hypervalent iodine. Issue 43 (26th October 2022)

• Record Type: Journal Article
• Authors: Declas, Nina; Maynard, John R. J.; Menin, Laure; Gasilova, Natalia; Götze, Sebastian; Sprague, Jakob L.; Stallforth, Pierre; Matile, Stefan; Waser, Jerome
• Is Part Of: Chemical science. Volume 13:Issue 43(2022)
• Page Start: 12808
• Page End: 12817
• Publication Date: 2022-10-26
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2sc04558c
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A tyrosine bioconjugation for the introduction of hypervalent iodine onto biomolecules is described. The transformation was applied to peptides and proteins and was used to modify native streptavidin to enable thiol-mediated cellular uptake. 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.