title: Brominated Luciferins Are Versatile Bioluminescent Probes.
abstract: We report a set of brominated luciferins for bioluminescence imaging. These regioisomeric scaffolds were accessed by using a common synthetic route. All analogues produced light with firefly luciferase, although varying levels of emission were observed. Differences in photon output were analyzed by computation and photophysical measurements. The brightest brominated luciferin was further evaluated in cell and animal models. At low doses, the analogue outperformed the native substrate in cells. The remaining luciferins, although weak emitters with firefly luciferase, were inherently capable of light production and thus potential substrates for orthogonal mutant enzymes.
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Steinhardt
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Rathbun
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Krull
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Yu
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: Jake
authors.initials: J
authors.lastname: Kwon
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: McCutcheon
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, 3205 McGaugh Hall, Irvine, CA, 92697, USA.
authors.forename: Krysten A
authors.initials: KA
authors.lastname: Jones
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.
authors.forename: Filipp
authors.initials: F
authors.lastname: Furche
authors.affiliation: Department of Chemistry, University of California, Irvine, 1120 Natural Sciences II, Irvine, CA, 92697, USA.|Department of Molecular Biology and Biochemistry, University of California, Irvine, 3205 McGaugh Hall, Irvine, CA, 92697, USA.|Department of Pharmaceutical Sciences, University of California, Irvine, 147 Bison Modular, Irvine, CA, 92697, USA.
authors.forename: Jennifer A
authors.identifier: http://orcid.org/0000-0002-9250-4702
authors.initials: JA
authors.lastname: Prescher
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D048888:Fireflies / Q000201:enzymology; D049454:Firefly Luciferin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D057809:HEK293 Cells; D054879:Halogenation; D006801:Humans; D007700:Kinetics; D008027:Light; D049409:Luciferases, Firefly / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D049454:Firefly Luciferin; D049409:Luciferases, Firefly
keywords: Appel's salt; bioluminescence; imaging; luciferase; luciferin