Recently, we investigated norbornene derivatives as cysteine sulfenic acid traps. In this strategy, the olefin reacts with the sulfenic acid through a strain-promoted group transfer reaction (Fig. ). This reaction was validated on small-molecule models, which revealed a higher reaction rate than dimedone. 7b A similar strategy has also been explored using cyclooctynes to trap sulfenic acids, 9 but these highly strained probes suffer from offtarget reactions, particularly with biological thiols. With less strain, norbornene is more selective than cyclooctynes. 7b Another benefit of the norbornene scaffold is that it is straightforward to synthesise and modify, enabling access to biotin-and alkyne-tagged derivatives such as 1 and 2 (norb-bio and norb-yne, respectively, Fig. ). Motivated by these promising small-molecule studies, 7b we carried out the first evaluation of norbornene derivatives as probes for cysteine sulfenic acid on proteins. Cysteine sulfenic acid was detected on a model protein, in HeLa cell lysates, and in living HeLa cells. Probes 1 and 2 displayed a different reactivity profile and superior selectivity when compared to a widely used dimedone probe-providing a new tool for the selective detection and analysis of cysteine sulfenic acid. Norbornene derivative 3 was first tested on the cysteine protease papain. Papain has a single free cysteine in its active site (Cys25) that can be oxidized with hydrogen peroxide to generate a model cysteine sulfenic acid. After optimization studies (S1-S12), papain was treated with probe 3 before adding H 2 O 2 (Fig. ) . After incubating for 1 hour at room temperature, the excess probe and oxidant were removed using a centrifugal concentrator.