title: Synthesis of Firefly Luciferin Analogues and Evaluation of the Luminescent Properties.
abstract: Five new firefly luciferin (1) analogues were synthesized and their light emission properties were examined. Modifications of the thiazoline moiety in 1 were employed to produce analogues containing acyclic amino acid side chains (2-4) and heterocyclic rings derived from amino acids (5 and 6) linked to the benzothiazole moiety. Although methyl esters of all of the synthetic derivatives exhibited chemiluminescence activity, only carboluciferin (6), possessing a pyrroline-substituted benzothiazole structure, had bioluminescence (BL) activity (λmax =547 nm). Results of bioluminescence studies with AMP-carboluciferin (AMP=adenosine monophosphate) and AMP-firefly luciferin showed that the nature of the thiazoline mimicking moiety affected the adenylation step of the luciferin-luciferase reaction required for production of potent BL. In addition, BL of 6 in living mice differed from that of 1 in that its luminescence decay rate was slower.
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, 223-8522, Yokohama, Japan.|Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, 223-8522, Yokohama, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ioka
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, 223-8522, Yokohama, Japan.|International Institute for Integrative Sleep Medicine (WPI-IIS), University of Tsukuba, Tennodai 1-1-1, Tsukuba-si, 305-8577, Ibaraki, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saitoh
authors.affiliation: Department of Engineering Science, The University of Electro-Communications, Chofugadake 1-5-1, Chofu, 182-8585, Tokyo, Japan.|Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Hirosawa 2-1, Wako, 351-0198, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iwano
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, 223-8522, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Engineering Science, The University of Electro-Communications, Chofugadake 1-5-1, Chofu, 182-8585, Tokyo, Japan.
authors.forename: Shojiro A
authors.initials: SA
authors.lastname: Maki
authors.affiliation: Laboratory for Cell Function Dynamics, Brain Science Institute, RIKEN, Hirosawa 2-1, Wako, 351-0198, Saitama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyawaki
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, 223-8522, Yokohama, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, 223-8522, Yokohama, Japan. nisiyama@chem.keio.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nishiyama
mesh_terms: D000249:Adenosine Monophosphate / Q000737:chemistry; D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry; D049454:Firefly Luciferin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D049409:Luciferases, Firefly / Q000378:metabolism; D049408:Luminescent Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D008163:Luminescent Measurements; D051379:Mice; D008822:Mice, Transgenic; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
chemical_list: D052160:Benzothiazoles; D049408:Luminescent Agents; D000249:Adenosine Monophosphate; D049454:Firefly Luciferin; D049409:Luciferases, Firefly; C005465:benzothiazole
keywords: biological activity; firefly luciferase; luminescence; structure-activity relationships; synthesis design