title: Detection and cellular imaging of human cancer enzyme using a turn-on, wavelength-shiftable, self-immolative profluorophore.
abstract: A frontier area in the development of activatable (turn-on) fluorescence-based probes is that concerned with rapid and selective stimulus triggering of probe activation so as to allow for biomarker identification and cellular imaging. The work here is concerned with a cloaked fluorophore composed of a reporter whose fluorescence is efficiently quenched by it being bound to an activatable trigger group through a novel self-immolative linker. Highly selective and rapid activation of the trigger group is achieved by chemical and enzymatic means that result in activated trigger group detachment from the self-immolative linker, with the latter subsequently cleaved from the reporter autonomously, thereby unmasking intense, red-shifted fluorescence emission. To achieve this success, we used a trimethyl-locked quinone propionic acid trigger group and an N-methyl-p-aminobenzyl alcohol self-immolative linker attached to the reporter. Delineated here are the synthesis and characterization of this cloaked fluorophore and the evaluation of its triggered turning on in the presence of an up-regulated enzyme in human cancer cells,
  quinone oxidoreductase-1 (NQO1, DT-diaphorase, EC 1.6.99.2).
authors.affiliation: Department of Chemistry, Louisiana State University , Baton Rouge, Louisiana 70803-1804, United States.
authors.forename: Suraj U
authors.initials: SU
authors.lastname: Hettiarachchi
authors.forename: Bijeta
authors.initials: B
authors.lastname: Prasai
authors.forename: Robin L
authors.initials: RL
authors.lastname: McCarley
mesh_terms: D005453:Fluorescence; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000378:metabolism*; D055668:Photochemical Processes
chemical_list: D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human