Synthesis of a Novel Symmetrical Photocleavable Group for the Efficient Capture and Release of Cysteine Sulfenic Acids on Oxidized Proteins From Streptavidin Beads

Cysteine sulfenic acids are thought to be key intermediates in protein oxidation but are difficult to study due to their high reactivity and transient nature. The beneficial properties of these oxidative events have been underexplored due to earlier studies primarily focusing on cell damage and death; however, increasing evidence suggests various physiological processes rely on these oxidative modifications. Previous work has shown that bicyclo[6.1.0]non-4-ynes (BCNs) can label sulfenic acids with high reaction kinetics via a pericyclic reaction, while also enabling copper-free click chemistry, allowing for a biotin-azide tag to be installed. However, due to the strong biotin- streptavidin interaction, these probes suffer from poor protein recovery and sub-optimal performance during mass-spectrometric analysis, respectively. Efforts towards incorporating the BCNs into a novel symmetrical photocleavable group based on 1,4-naphthoquinone, or their use in combination with photocleavable biotin-azide are proposed to improve upon these limitations and are presented in this thesis.