Biotin-ANP-Ub-PA (UbiQ-077) is an activity-based probe for deubiquitinating enzymes (DUBs), in which the N-terminal biotin tag is linked to the Ub protein through a UV cleavable ANP linker (Figure 1). UbiQ-077 allows one to use the powerful biotin affinity tag but also to release any covalently bound Ub-DUB complexes under milder (photolysis) conditions. Note that the propargyl amide (PA) electrophile forms an acid labile bond with the active site cysteine of a DUB (Fig 2), allowing deconjugation of the Ub-DUB complex if required.

Figure 1. UV cleavable linker ANP= 3-amino-3-(2-nitrophenyl)propanoic acid

Literature. (1) Rodenko et al. Nat Prot 2006, 1, 1120. (2) Aoki et al Bioorg Med Chem. 2009, 17, 3405. (3) Ekkebus et al. J Am Chem Soc 2013, 135, 2867. (4) Sommer et al. Bioorg Med Chem. 2013, 21, 2511.