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

Abstract

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 cyste-ine protease cathepsin B. We here report that the non-natural amino acid pipecolinic acid in the P2 position of sub-strates and chemical probes leads to improved selectivity towards MALT1 and results in cell permeable fluorescent probes.