LAUSR

Abstract A fluorescent probe for protease sensing and based on the “covalent-assembly” principle is reported. The basic rational for this unusual class of chemodosimeters proposed by the Anslyn and Yang groups entails the synthesis of non-fluorophore caged precursors full-stable and reactive towards the targeted analyte. Unlike the first generation of protease-sensitive “covalent-assembly” type probes recently published by ourselves ( Org. Biomol. Chem. 2017 , 15 , 2575–2584), the availability of dicyanomethylidenyl and enzyme-labile phenylacetamide moieties within the core structure of mixed bis-aryl ether 2 enables its rapid conversion into a fluorescent pyronin dye at physiological pH and upon activation with penicillin G acylase (PGA). This is real progress towards the practical implementation of this ingenious activation mechanism to the detection of enzymes in their native environment ( in cellulo or in vivo ).