We announce the launch of an activity-based probe that is designed to selectively target USP7: UbiQ-314. Reported by Gjonaj et al. (Chem Comm 2019, 55, 5075), probe UbiQ-314 is based on Ub with the following mutations: T7D, L8Y, I13R, E34L, Q40N, L69A, and L71A.

• residue Lys58 contains a biotin tag which, besides detection and binding, also serves to increase USP7 selectivity by prohibiting binding of most USPs

• the N-terminus is functionalised with a 5-carboxyrhodamine110 dye (cRh110, exc/emi 480/520 nm) allowing for sensitive (and fast in-gel fluorescence) detection

• a cysteine residue is introduced between the dye and N-terminus for further modification with thiol-reactive tags

• UbiQ-314 contains a C-terminal propargyl amide (PA) warhead, which forms a covalent linkage with the active site Cys of USP7 that can be cleaved by acid treatment (5% aq. TFA), allowing for proteomic analyses.