Use of Non-Natural Amino Acids for the Design and Synthesis of a Selective, Cell-Permeable MALT1 Activity-Based Probe

Constitutive proteolytic activity
of MALT1 is associated with highly
aggressive B-cell lymphomas. Chemical tools that detect active MALT1
have been reported, but suffer from poor cell permeability and/or
cross-reactivity with the cysteine protease cathepsin B. Here, we
report that the non-natural amino acid pipecolinic acid in the P2
position of substrates and chemical probes leads to improved selectivity
toward MALT1 and results in cell-permeable fluorescent probes.