1,2-Allenic Ketone-Based Fluorogenic Probes for Imaging of S-Sulfinylation in Living Cells

Abstract

Cysteine S-sulfinylation is an important oxidative post-translational modification on proteins that regulates a variety of cell and protein functions. Aberrant S-sulfinylation contributes to a range of human pathologies, such as cancer and cardiovascular disease. However, efforts to elucidate the roles of S-sulfinylation in physiology and disease have been hampered due to the lack of methodology for the selective and direct monitoring of this modification in living cells. In this work, we developed a fluorogenic probe PAK for sulfinic acids by using 1,2-allenic ketone as the recognition moiety. The addition of sulfinic acids to the probe affords β,γ-unsaturated enones, which inhibits the photoinduced electron transfer process within the probe and thus affords a turn-on fluorescence response. Although biothiols can also react with PAK, they give weakly emissive α,β-unsaturated enones and thus would not interfere with the fluorescence detection of sulfinic acids. The probe PAK shows good selectivity and sensitivity toward sulfinic acids and has been used for imaging of sulfinic acid modifications under oxidative stress conditions in living cells. Moreover, the close relationship between S-sulfinylation and reactive oxygen species levels in living cells has been confirmed by the present probe.