title: Virginia Orange: A Versatile, Red-Shifted Fluorescein Scaffold for Single- and Dual-Input Fluorogenic Probes.
abstract: Fluorogenic molecules are important tools for biological and biochemical research. The majority of fluorogenic compounds have a simple input-output relationship, where a single chemical input yields a fluorescent output. Development of new systems where multiple inputs converge to yield an optical signal could refine and extend fluorogenic compounds by allowing greater spatiotemporal control over the fluorescent signal. Here, we introduce a new red-shifted fluorescein derivative, Virginia Orange, as an exceptional scaffold for single- and dual-input fluorogenic molecules. Unlike fluorescein, installation of a single masking group on Virginia Orange is sufficient to fully suppress fluorescence, allowing preparation of fluorogenic enzyme substrates with rapid, single-hit kinetics. Virginia Orange can also be masked with two independent moieties; both of these masking groups must be removed to induce fluorescence. This allows facile construction of multi-input fluorogenic probes for sophisticated sensing regimes and genetic targeting of latent fluorophores to specific cellular populations.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute , 19700 Helix Drive, Ashburn, Virginia 20147, United States.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Grimm
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute , 19700 Helix Drive, Ashburn, Virginia 20147, United States.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Gruber
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute , 19700 Helix Drive, Ashburn, Virginia 20147, United States.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ortiz
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute , 19700 Helix Drive, Ashburn, Virginia 20147, United States.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Brown
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute , 19700 Helix Drive, Ashburn, Virginia 20147, United States.
authors.forename: Luke D
authors.initials: LD
authors.lastname: Lavis
mesh_terms: D000818:Animals; D055162:Biocatalysis; D019556:COS Cells; D002522:Chlorocebus aethiops; D019793:Fluorescein / Q000737:chemistry* / Q000378:metabolism; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D061848:Optical Imaging
chemical_list: D005456:Fluorescent Dyes; D019793:Fluorescein