title: In situ formation of pyronin dyes for fluorescence protease sensing.
abstract: We report a reaction-based strategy for the fluorogenic detection of protease activity. Based on the "covalent-assembly" probe design principle recently put forward by the Yang group for detection of Sarin related threats (J. Am. Chem. Soc., 2014, 136, 6594-6597), we have designed two unusual non-fluorescent caged precursors (mixed bis-aryl ethers) which are readily converted into a fluorescent unsymmetrical pyronin dye through a domino cyclisation-aromatisation reaction triggered by penicillin G acylase (PGA) or leucine aminopeptidase (LAP). Fluorescence-based in vitro assays and HPLC-fluorescence/-MS analyses support the claimed activation mechanism whose the further implementation to "smart" imaging agents for the study of protease function in vivo is expected.
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302, CNRS, Univ. Bourgogne Franche-Comté, 9, Avenue Alain Savary, 21078 Dijon, France. anthony.romieu@u-bourgogne.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Debieu
authors.affiliation: Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302, CNRS, Univ. Bourgogne Franche-Comté, 9, Avenue Alain Savary, 21078 Dijon, France. anthony.romieu@u-bourgogne.fr and Institut Universitaire de France, 103, boulevard Saint-Michel, 75005 Paris, France.
authors.forename: Anthony
authors.identifier: http://orcid.org/0000-0002-2300-4499
authors.initials: A
authors.lastname: Romieu
mesh_terms: D002851:Chromatography, High Pressure Liquid; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry*; D013058:Mass Spectrometry; D015394:Molecular Structure; D010447:Peptide Hydrolases / Q000032:analysis* / Q000378:metabolism; D011754:Pyronine / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D010447:Peptide Hydrolases; D011754:Pyronine