Generation of a quenched phosphonate activity-based probe for labelling the active KLK7 protease

Kallikrein 7 (KLK7) is a chymotrypsin-like serine protease with established roles in skin diseases like the rare Netherton syndrome, an overdesquamating and inflammatory condition, but also common atopic dermatitis, and a potential drug target for these and possibly other diseases. Nevertheless, tools to determine the active KLK7 enzyme are not available. Here, a mixed alkyl aryl phosphonate quenched activity-based probe that detects the active KLK7 was developed and evaluated in vitro . This KLK7-qABP can potentially be used to monitor KLK7 activity in vivo . A mixed alkyl aryl phosphonate qABP for KLK7 was developed where the internally-quenching system is realeased upon binding of the qABP to the active enzyme.