Visible-Light-Induced Cysteine-Specific Bioconjugation: Biocompatible Thiol-Ene Click Chemistry

Abstract

© 2020 Wiley-VCH GmbH. Bioconjugation methods using visible-light photocatalysis have emerged as powerful synthetic tools for the selective modification of biomolecules under mild reaction conditions. However, the number of photochemical transformations that allow successful protein bioconjugation is still limited because of the need for stringent reaction conditions. Herein, we report that a newly developed water-compatible fluorescent photosensitizerQ(PEG)can be used for visible-light-induced cysteine-specific bioconjugation for the installation ofQ(PEG)by exploiting its intrinsic photosensitizing ability to activate the S-H bond of cysteine. The slightly modifiedQ(CAT)enables the effective photocatalytic cysteine-specific conjugation of biologically relevant groups. The superior reactivity and cysteine selectivity of this methodology was further corroborated by traceless bioconjugation with a series of complex peptides and proteins under biocompatible conditions