Kinetics improvement of protease-mediated formation of pyronin dyes

Sylvain Debieu (1) , Anthony Romieu (1, 2)

1 ICMUB - Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon]
2 IUF - Institut universitaire de France

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).

Mots clés: Biocompatible reaction; Covalent assembly; Fluorescent probe; Protease; Pyronin; Xanthene dyes; large stokes shift; emitting fluorescent-probe; in-situ formation; turn-on probe; alkaline-phosphatase activity; living cells; selective detection; hydrogen-sulfide; signaling mechanism; sensitive detection

Domaines: Chimie; Chimie organique

Sylvain Debieu, Anthony Romieu. Kinetics improvement of protease-mediated formation of pyronin dyes. Tetrahedron Letters, 2018, 59 (20), pp.1940 - 1944. ⟨10.1016/j.tetlet.2018.04.010⟩. ⟨hal-01856701⟩