Superoxide-responsive quinone methide precursor (qmp-so) and method of use

Abstract

The present invention discloses superoxide-specific quinone methide precursors (QMP-SOs) that enable proximity labeling and chemoproteomics to investigate superoxide redox biology. QMP-SOs are activated by superoxide to generate a reactive quinone methide intermediate that covalently tags nearby proteins. These probes exhibit high selectivity toward superoxide over other ROS, enabling protein labeling in superoxide-rich cellular compartments. QMP-SOs are compatible with fluorescence imaging and tandem mass tag (TMT)-based mass spectrometry, facilitating visualization of superoxide dynamics and identification of superoxide-regulated proteins. In menadione-treated HepG2 cells, QMP-SO-TMT profiling identified mitochondrial proteins including DJ-1 and DLDH as redox-sensitive targets, linking superoxide stress to cell survival and metabolism. The QMP-SO platform uniquely combines spatial proximity labeling with superoxide specificity, allowing previously inaccessible insights into dynamic and localized redox signaling. This invention is broadly applicable in studying superoxide-mediated processes and holds potential for therapeutic target discovery in diseases driven by oxidative stress, including cancer, aging, and neurodegeneration.

Dependencies are inferred from the claim text.