Mild oxidation can convert the sulfhydryl group of cysteine residues on proteins to cysteine-sulfenic acid derivatives (Cys-SOH). Protein sulfenylation, then, is a post-translational modification that is relevant to redox signaling. DYn-2 is a chemoselective probe for detecting sulfenylated proteins in intact cells. DYn-2 consists of 1,3-cyclohexanedione coupled to an alkyne moiety by a 3-carbon spacer. The cyclohexanedione group selectively reacts with protein sulfenic acid modifications. The alkyne group of DYn-2 can then be detected using azide-bearing tags by standard click chemistry. This approach offers superior sensitivity relative to using azide-modified probes with alkynyl detection tags.