title: cybLuc: An Effective Aminoluciferin Derivative for Deep Bioluminescence Imaging.
abstract: To enhance the efficiency of firefly luciferase/luciferin bioluminescence imaging, a series of N-cycloalkylaminoluciferins (cyaLucs) were developed by introducing lipophilic N-cycloalkylated substitutions. The experimental results demonstrate that these cyaLucs are effective substrates for native firefly luciferase (Fluc) and can produce elevated bioluminescent signals in vitro, in cellulo, and in vivo. It should be noted that, in animal studies, N-cyclobutylaminoluciferin (cybLuc) at 10 μM (0.1 mL), which is 0.01% of the standard dose of d-luciferin (dLuc) used in mouse imaging, can radiate 20-fold more bioluminescent light than d-luciferin (dLuc) or aminoluciferin (aLuc) at the same concentration. Longer in vivo emission imaging using cybLuc suggests that it can be used for long-time observation. Regarding the mechanism of cybLuc, our cocrystal structure data from firefly luciferase with oxidized cybLuc suggested that oxidized cybLuc fits into the same pocket as oxyluciferin. Most interestingly, our results demonstrate that the sensitivity of cybLuc in brain tumor imaging contributes to its extended application in deep tissues.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Wenxiao
authors.initials: W
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University , Jinan, Shandong 250100, China.|Faculty of Light Industry, Province Key Laboratory of Microbial Engineering, Qilu University of Technology , Jinan, Shandong 250353, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Chunchao
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Haixiu
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Tianchao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University , Jinan, Shandong 250100, China.
authors.forename: Zenglin
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Faculty of Light Industry, Province Key Laboratory of Microbial Engineering, Qilu University of Technology , Jinan, Shandong 250353, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Huateng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center , Houston, Texas 77030, United States.
authors.forename: Yubin
authors.identifier: 0000-0001-7962-0517
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Lupei
authors.identifier: 0000-0003-0531-8985
authors.initials: L
authors.lastname: Du
authors.affiliation: State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University , Jinan, Shandong 250100, China.
authors.forename: Lichuan
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.
authors.forename: Minyong
authors.identifier: 0000-0003-3276-4921
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D049454:Firefly Luciferin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000737:chemistry; D049408:Luminescent Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D008807:Mice, Inbred BALB C
chemical_list: D049408:Luminescent Agents; D049454:Firefly Luciferin; D008156:Luciferases