研究者詳細 - 花岡　健二郎

論文 - 花岡　健二郎

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Method for enhancing cell penetration of Gd <sup>3+</sup>-based MRI contrast agents by conjugation with hydrophobic fluorescent dyes

Yamane T., Hanaoka K., Muramatsu Y., Tamura K., Adachi Y., Miyashita Y., Hirata Y., Nagano T.

Bioconjugate Chemistry （Bioconjugate Chemistry） 22 （ 11 ） 2227 - 2236 2011年11月

研究論文（学術雑誌）, 査読有り, ISSN 10431802

Gadolinium ion (Gd 3+) complexes are commonly used as magnetic resonance imaging (MRI) contrast agents to enhance signals in T 1-weighted MR images. Recently, several methods to achieve cell-permeation of Gd 3+ complexes have been reported, but more general and efficient methodology is needed. In this report, we describe a novel method to achieve cell permeation of Gd 3+ complexes by using hydrophobic fluorescent dyes as a cell-permeability-enhancing unit. We synthesized Gd 3+ complexes conjugated with boron dipyrromethene (BDP-Gd) and Cy7 dye (Cy7-Gd), and showed that these conjugates can be introduced efficiently into cells. To examine the relationship between cell permeability and dye structure, we further synthesized a series of Cy7-Gd derivatives. On the basis of MR imaging, flow cytometry, and ICP-MS analysis of cells loaded with Cy7-Gd derivatives, highly hydrophobic and nonanionic dyes were effective for enhancing cell permeation of Gd 3+ complexes. Furthermore, the behavior of these Cy7-Gd derivatives was examined in mice. Thus, conjugation of hydrophobic fluorescent dyes appears to be an effective approach to improve the cell permeability of Gd 3+ complexes, and should be applicable for further development of Gd 3+-based MRI contrast agents. © 2011 American Chemical Society.

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Development of a potassium ion-selective fluorescent sensor based on 3-styrylated BODIPY

Hirata T., Terai T., Komatsu T., Hanaoka K., Nagano T.

Bioorganic and Medicinal Chemistry Letters （Bioorganic and Medicinal Chemistry Letters） 21 （ 20 ） 6090 - 6093 2011年10月

研究論文（学術雑誌）, 査読有り, ISSN 0960894X

We have developed a red-emitting fluorescent K + probe, B3TAC, which also shows a wavelength shift upon binding to K +. The probe was synthesized by conjugating a cryptand-based chelator, 2-triazacryptand [2,2,3-1-(2-methoxyethoxy)benzene (TAC), to position 3 of the BODIPY fluorophore through a styryl linker. In water-acetonitrile mixed solvent, it responded to K + in the physiological concentration range with high selectivity over Na + and other metal ions. B3TAC is potentially useful for measuring cellular K + ion concentration, as well as for simple, naked-eye detection of K + in solution. © 2011 Elsevier Ltd. All rights reserved.

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Rational design of boron dipyrromethene (BODIPY)-based photobleaching- resistant fluorophores applicable to a protein dynamics study

Komatsu T., Oushiki D., Takeda A., Miyamura M., Ueno T., Terai T., Hanaoka K., Urano Y., Mineno T., Nagano T.

Chemical Communications （Chemical Communications） 47 （ 36 ） 10055 - 10057 2011年09月

研究論文（学術雑誌）, 査読有り, ISSN 13597345

We studied the photobleaching of a library of boron dipyrromethene (BODIPY) derivatives with a range of electron densities, and found that the photobleaching rate is influenced by the electron-withdrawing capacity of the substituents. Electron-deficient BODIPYs generated less singlet oxygen, were less reactive to singlet oxygen, and were highly resistant to photobleaching. We confirmed the utility of one of these fluorophores, 2,6-diCO2R-BDP, for visualizing EGF receptor dynamics in cells expressing an SNAP-tagged EGF receptor. © The Royal Society of Chemistry 2011.

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Development of a far-red to near-infrared fluorescence probe for calcium ion and its application to multicolor neuronal imaging

Egawa T., Hanaoka K., Koide Y., Ujita S., Takahashi N., Ikegaya Y., Matsuki N., Terai T., Ueno T., Komatsu T., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 133 （ 36 ） 14157 - 14159 2011年09月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

To improve optical imaging of Ca 2+ and to make available a distinct color window for multicolor imaging, we designed and synthesized CaSiR-1, a far-red to near-infrared fluorescence probe for Ca 2+, using Si-rhodamine (SiR) as the fluorophore and the well-known Ca 2+ chelator BAPTA. This wavelength region is advantageous, affording higher tissue penetration, lower background autofluorescence, and lower phototoxicity in comparison with the UV to visible range. CaSiR-1 has a high fluorescence off/on ratio of over 1000. We demonstrate its usefulness for multicolor fluorescence imaging of action potentials (visualized as increases in intracellular Ca 2+) in brain slices loaded with sulforhodamine 101 (red color; specific for astrocytes) that were prepared from transgenic mice in which some neurons expressed green fluorescent protein. © 2011 American Chemical Society.

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Development of a highly selective fluorescence probe for alkaline phosphatase

Kawaguchi M., Hanaoka K., Komatsu T., Terai T., Nagano T.

Bioorganic and Medicinal Chemistry Letters （Bioorganic and Medicinal Chemistry Letters） 21 （ 17 ） 5088 - 5091 2011年09月

研究論文（学術雑誌）, 査読有り, ISSN 0960894X

We have developed the first highly selective fluorescence probe for alkaline phosphatase (ALP), TG-mPhos. This probe shows selectivity for ALP over protein tyrosine phosphatase and protein serine/threonine phosphatase. Our previously developed TG-Phos, which has a phenolic phosphate linkage in place of the alcoholic phosphate linkage of TG-mPhos, lacks this selectivity. TG-mPhos should enable precise fluorescence imaging of ALP activity in biological applications. © 2011 Elsevier Ltd. All rights reserved.

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Fluorescence probe for lysophospholipase C/NPP6 activity and a potent NPP6 inhibitor

Kawaguchi M., Okabe T., Okudaira S., Hanaoka K., Fujikawa Y., Terai T., Komatsu T., Kojima H., Aoki J., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 133 （ 31 ） 12021 - 12030 2011年08月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that have a role in regulating extracellular nucleotide and phospholipid metabolism. Among the members of the NPP family, NPP1 and -3 act on nucleotides such as ATP, while NPP2, -6, and -7 act on phospholipids such as lysophosphatidylcholine and sphingomyelin. NPP6, a recently characterized NPP family member, is a choline-specific glycerophosphodiester phosphodiesterase, but its functions remain to be analyzed, partly due to the lack of highly sensitive activity assay systems and practical inhibitors. Here we report synthesis of novel NPP6 fluorescence probes, TG-mPC and its analogues TG-mPC 3C, TG-mPC 5C, TG-mPENE, TG-mPEA, TG-mPhos, TG-mPA, TG-mPMe, and TG-mPPr. Among the seven NPPs, only NPP6 hydrolyzed TG-mPC, TG-mPC 3C, and TG-mPENE. TG-mPC was hydrolyzed in the cell lysate from NPP6-transfected cells, but not control cells, showing that it is suitable for use in cell-based NPP6 assays. We also examined the usefulness of TG-mPC as a fluorescence imaging probe. We further applied TG-mPC to carry out high-throughput NPP6 inhibitor screening and found several NPP6-selective inhibitors in a library of about 80 000 compounds. Through structure-activity relationship (SAR) analysis, we identified a potent and selective NPP6 inhibitor with an IC 50 value of 0.21 μM. Our NPP6-selective fluorescence probe, TG-mPC, and the inhibitor are expected to be useful to elucidate the biological function of NPP6. © 2011 American Chemical Society.

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Development of a highly sensitive fluorescence probe for hydrogen peroxide

Abo M., Urano Y., Hanaoka K., Terai T., Komatsu T., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 133 （ 27 ） 10629 - 10637 2011年07月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

Hydrogen peroxide is believed to play a role in cellular signal transduction by reversible oxidation of proteins. Here, we report the design and synthesis of a novel fluorescence probe for hydrogen peroxide, utilizing a photoinduced electron transfer strategy based on benzil chemistry to control the fluorescence. The practical value of this highly sensitive and selective fluorescence probe, NBzF, was confirmed by its application to imaging of hydrogen peroxide generation in live RAW 264.7 macrophages. NBzF was also employed for live cell imaging of hydrogen peroxide generated as a signaling molecule in A431 human epidermoid carcinoma cells. © 2011 American Chemical Society.

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Aminoluciferins as functional bioluminogenic substrates of firefly luciferase

Takakura H., Kojima R., Urano Y., Terai T., Hanaoka K., Nagano T.

Chemistry - An Asian Journal （Chemistry - An Asian Journal） 6 （ 7 ） 1800 - 1810 2011年07月

研究論文（学術雑誌）, 査読有り, ISSN 18614728

Firefly luciferase is widely used as a reporter gene in assays to study gene expression, gene delivery, and so on because of its extremely high signal-to-noise ratio. The availability of a range of bioluminogenic substrates would greatly extend the applicability of the luciferin-luciferase system. Herein, we describe a design concept for functional bioluminogenic substrates based on the aminoluciferin (AL) scaffold, together with a convenient, high-yield method for synthesizing N-alkylated ALs. We confirmed the usefulness of ALs as bioluminogenic substrates by synthesizing three probes. The first was a conjugate of AL with glutamate, Glu-AL. When Glu-AL, the first membrane-impermeable bioluminogenic substrate of luciferases, was applied to cells transfected with luciferase, luminescence was not observed; that is, by using Glu-AL, we can distinguish between intracellular and extracellular events. The second was Cy5-AL, which consisted of Cy5, a near-infrared (NIR) cyanine fluorescent dye, and AL, and emitted NIR light. When Cy5-AL reacted with luciferase, luminescence derived from Cy5 was observed as a result of bioluminescence resonance energy transfer (BRET) from AL to Cy5. The NIR emission wavelength would allow a signal to be observed from deeper tissues in bioluminescence in vivo imaging. The third was biotin-DEVD-AL (DEVD=the amino acid sequence Asp-Glu-Val-Asp), which employed a caspase-3 substrate peptide as a switch to control the accessibility of the substrate to luciferase, and could detect the activity of caspase-3 in a time-dependent manner. This generalized design strategy should be applicable to other proteases. Our results indicate that the AL scaffold is appropriate for a range of functional luminophores and represents a useful alternative substrate to luciferin. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Evolution of group 14 rhodamines as platforms for near-infrared fluorescence probes utilizing photoinduced electron transfer

Koide Y., Urano Y., Hanaoka K., Terai T., Nagano T.

ACS Chemical Biology （ACS Chemical Biology） 6 （ 6 ） 600 - 608 2011年06月

研究論文（学術雑誌）, 査読有り, ISSN 15548929

The absorption and emission wavelengths of group 14 pyronines and rhodamines, which contain silicon, germanium, or tin at the 10 position of the xanthene chromophore, showed large bathochromic shifts compared to the original rhodamines, owing to stabilization of the LUMO energy levels by σ *-π * conjugation between group 14 atom-C (methyl) σ * orbitals and a π * orbital of the fluorophore. These group 14 pyronines and rhodamines retain the advantages of the original rhodamines, including high quantum efficiency in aqueous media (φ fl = 0.3-0.45), tolerance to photobleaching, and high water solubility. Group 14 rhodamines have higher values of reduction potential than other NIR light-emitting original rhodamines, and therefore, we speculated their NIR fluorescence could be controlled through the photoinduced electron transfer (PeT) mechanism. Indeed, we found that the fluorescence quantum yield (φ fl) of Si-rhodamine (SiR) and Ge-rhodamine (GeR) could be made nearly equal to zero, and the threshold level for fluorescence on/off switching lies at around 1.3-1.5 V for the SiRs. This is about 0.1 V lower than in the case of TokyoGreens, in which the fluorophore is well established to be effective for PeT-based probes. That is to say, the fluorescence of SiR and GeR can be drastically activated by more than 100-fold through a PeT strategy. To confirm the validity of this strategy for developing NIR fluorescence probes, we employed this approach to design two kinds of novel fluorescence probes emitting in the far-red to NIR region, i.e., a series of pH-sensors for use in acidic environments and a Zn 2+ sensor. We synthesized these probes and confirmed that they work well. © 2011 American Chemical Society.

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Development of an Si-rhodamine-based far-red to near-infrared fluorescence probe selective for hypochlorous acid and its applications for biological imaging

Koide Y., Urano Y., Hanaoka K., Terai T., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 133 （ 15 ） 5680 - 5682 2011年04月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

A far-red to near-infrared (NIR) fluorescence probe, MMSiR, based on Si-rhodamine, was designed and synthesized for sensitive and selective detection of HOCl in real time. MMSiR and its oxidized product SMSiR have excellent properties, including pH-independence of fluorescence, high resistance to autoxidation and photobleaching, and good tissue penetration of far-red to NIR fluorescence emission. The value of MMSiR was confirmed by real-time imaging of phagocytosis using a fluorescence microscope. wsMMSiR, a more hydrophilic derivative of MMSiR, permitted effective in vivo imaging of HOCl generation in a mouse peritonitis model. This probe is expected to be a useful tool for investigating the wide range of biological functions of HOCl. © 2011 American Chemical Society.

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Positive correlation between the generation of reactive oxygen species and activation/reactivation of transgene expression after hydrodynamic injections into mice

Takiguchi N., Takahashi Y., Nishikawa M., Matsui Y., Fukuhara Y., Oushiki D., Kiyose K., Hanaoka K., Nagano T., Takakura Y.

Pharmaceutical Research （Pharmaceutical Research） 28 （ 4 ） 702 - 711 2011年04月

研究論文（学術雑誌）, 査読有り, ISSN 07248741

Purpose: Hydrodynamic injection has been shown to reactivate silenced transgene expression in mouse liver. In this study, the roles of inflammatory cytokines and reactive oxygen species (ROS) in the reactivation were examined. Methods: Production of inflammatory cytokines and ROS by hydrodynamic injection of saline was examined in mice that had received a hydrodynamic injection of a plasmid expressing Gaussia luciferase. The level of reporter gene expression was used as an indicator of the reactivation. The involvement of cytokines and ROS was examined by depleting Kupffer cells or by pre-administration of antioxidants, respectively. Results: A hydrodynamic injection of saline induced a significant production of interleukin (IL)-6. Depleting Kupffer cells using clodronate liposomes markedly reduced the IL-6 production but had no significant effect on the transgene expression. On the other hand, an injection of catalase or N-acetylcysteine significantly inhibited the hydrodynamic injection-induced reactivation of silenced transgene expression. The silenced expression was also reactivated by carbon tetrachloride, an inducer of oxidative stress in the liver, in a dose-dependent manner, and this reactivation was significantly inhibited by catalase. Conclusions: These findings show a positive correlation between the generation of ROS and the reactivation of silenced transgene expression after hydrodynamic injections. © 2010 Springer Science+Business Media, LLC.

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Development of a fluorescein analogue, TokyoMagenta, as a novel scaffold for fluorescence probes in red region

Egawa T., Koide Y., Hanaoka K., Komatsu T., CooTeraiper T., Nagano T.

Chemical Communications （Chemical Communications） 47 （ 14 ） 4162 - 4164 2011年03月

研究論文（学術雑誌）, 査読有り, ISSN 13597345

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Rational design of ratiometric near-infrared fluorescent pH probes with various pK<inf>a</inf> values, based on aminocyanine

Myochin T., Kiyose K., Hanaoka K., Kojima H., Terai T., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 133 （ 10 ） 3401 - 3409 2011年03月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

Novel ratiometric, near-infrared fluorescent pH probes with various pK a values have been designed and synthesized on the basis of aminocyanine bearing a diamine moiety, and their photochemical properties were evaluated. Under acidic conditions, these pH probes showed a 46- to 83-nm red shift of the absorption maximum. This change is sufficiently large to permit their use as ratiometric pH probes, and is reversible, whereas monoamine-substituted aminocyanines showed irreversible changes because of their instability under acidic conditions. Furthermore, the pKa values of these probes can be predicted from the calculated pKa values of the diamine moieties, obtained from the SciFinder database. This design strategy is very simple and flexible, and should be applicable to develop NIR pH probes for various applications. © 2011 American Chemical Society.

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Design and synthesis of a novel fluorescence probe for Zn<sup>2+</sup> based on the spirolactam ring-opening process of rhodamine derivatives

Sasaki H., Hanaoka K., Urano Y., Terai T., Nagano T.

Bioorganic and Medicinal Chemistry （Bioorganic and Medicinal Chemistry） 19 （ 3 ） 1072 - 1078 2011年02月

研究論文（学術雑誌）, 査読有り, ISSN 09680896

The spirolactam ring-opening process of rhodamine derivative is one of the most useful mechanisms for controlling fluorescence properties. However, the open/closed equilibrium reaction of rhodamine spirolactam has not been well characterized. Therefore, we examined the relationship between the spirolactam ring-opening process of rhodamine derivatives and the structure of the xanthene moiety. Based on the results of this investigation, we selected a candidate xanthene moiety for a Zn2+ sensor, and successfully developed a new fluorescence probe for Zn2+. © 2010 Elsevier Ltd. All rights reserved.

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A time-resolved fluorescence probe for dipeptidyl peptidase 4 and its application in inhibitor screening

Kawaguchi M., Okabe T., Terai T., Hanaoka K., Kojima H., Minegishi I., Nagano T.

Chemistry - A European Journal （Chemistry - A European Journal） 16 （ 45 ） 13479 - 13486 2010年12月

研究論文（学術雑誌）, 査読有り, ISSN 09476539

The prevalence of type 2 diabetes is increasing dramatically throughout the world. Recently, dipeptidyl peptidase 4 (DPP4) was identified as a potential antidiabetes target. Many DPP4 inhibitors, such as sitagliptin and vildagliptin, have been developed and marketed, but superior therapeutic agents are still required. Therefore, we have developed new methodology for screening of DPP4 inhibitors. Absorption-based measurements with para-nitroaniline or fluorescence-based measurements with the coumarin derivative 7-amino-4-methylcoumarin are often used for the screening of protease inhibitors, including DPP4 inhibitors, but these strategies are not sufficiently sensitive because of interfering background absorption and fluorescence, thus giving rise to many false-positive and false-negative results. Therefore, we have designed and synthesised a novel DPP4 probe (Gly-Pro-BCD-Tb; Gly=glycine, Pro=proline, andBCD defines the backbone of the probe comprising an aniline derivative as on/off switch, a 7-amino-4-methyl-2(1H)-quinolinone (cs-124) as antenna moiety, and a diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA) as chelator moiety, Tb=terbium) for time-resolved fluorescence (TRF) measurements. TRF measurements with Gly-Pro-BCD-Tb showed high sensitivity and reliability in the inhibitory assay relative to Gly-Pro-MCA (MCA=4- methylcoumarin-7-amide), a conventional fluorescence probe for DPP4. Further, we employed our probe for high-throughput DPP4 inhibitor screening with 3841 randomly selected compounds and found that epibestatin, an epimer of bestatin (a well-known anticancer drug and general aminopeptidase inhibitor), showed dose-dependent DPP4 inhibitory activity. Interestingly, bestatin did not exhibit DPP4 inhibitory activity. We believe that this screening system will be useful for the discovery of DPP4 inhibitors with novel structural scaffolds. Reliable and highly sensitive inhibitor screening has been realised through the synthesis of a novel dipeptidyl peptidase 4 (DPP4) probe (see picture). The inhibitor screening employed high-throughput time-resolved fluorescence (TRF) measurements and identified epibestatin as a DPP4 inhibitor. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Hypoxia-sensitive fluorescent probes for in vivo real-time fluorescence imaging of acute ischemia

Kiyose K., Hanaoka K., Oushiki D., Nakamura T., Kajimura M., Suematsu M., Nishimatsu H., Yamane T., Terai T., Hirata Y., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 132 （ 45 ） 15846 - 15848 2010年11月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

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Development of responsive lanthanide-based magnetic resonance imaging and luminescent probes for biological applications

Hanaoka K.

Chemical and Pharmaceutical Bulletin （Chemical and Pharmaceutical Bulletin） 58 （ 10 ） 1283 - 1294 2010年10月

研究論文（学術雑誌）, 査読有り, ISSN 00092363

Lanthanide complexes have unique chemical characteristics compared with typical organic complexes, and have recently attracted much interest because of the expanding need for new bioanalytical sensors. For example, magnetic resonance imaging (MRI) permits noninvasive three-dimensional imaging inside opaque organisms, and gadolinium ion (Gd3+) complexes have become important tools as MRI contrast agents. However, most of them are nonspecific, and report solely on anatomy. Therefore, responsive MRI contrast agents, so-called "smart" MRI contrast agents whose ability to relax water protons is greatly enhanced by recognition of a particular biomolecule, have great potential for elucidating biological phenomena. On the other hand, lanthanide complexes such as europium (Eu3+) and terbium (Tb 3+) complexes have excellent luminescence properties for biological applications, i.e., long luminescence lifetime of the order of milliseconds and a large Stoke's shift of >200 nm. Their long-lived luminescence is especially suitable for time-resolved measurements, because the interference from short-lived background fluorescence and scattered light rapidly decays to a negligible level after a pulse of excitation light is applied, and the emitted light can be collected after an appropriate delay time. These luminescent lanthanide complexes have already found commercial use as highly sensitive luminescent probes in heterogeneous and homogeneous assays. This paper reviews our research on the design and synthesis of responsive lanthanide-based MRI and luminescent probes for advanced bioimaging. © 2010 Pharmaceutical Society of Japan.

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Development of luciferin analogues bearing an amino group and their application as BRET donors

Takakura H., Sasakura K., Ueno T., Urano Y., Terai T., Hanaoka K., Tsuboi T., Nagano T.

Chemistry - An Asian Journal （Chemistry - An Asian Journal） 5 （ 9 ） 2053 - 2061 2010年09月

研究論文（学術雑誌）, 査読有り, ISSN 18614728

We systematically synthesized bioluminogenic substrates bearing an amino group on benzothiazole, quinoline, naphthalene, and coumarin scaffolds. They emit bioluminescence in various colors: red, orange, yellow, and green. An amino-substituted cou-marylluciferin derivative, coumarylami-noluciferin (CAL), showed the shortest bioluminescence wavelength among substrates reported so far. Further, the fluorescence of CAL did not exhibit solvatochromism, which suggests that its bioluminescence is not susceptible to environmental factors. We applied CAL as an energy-donor substrate for a bioluminescence resonance energy transfer (BRET) system with click beetle red luciferase (CBRluc), a mutant of firefly luciferase, as the energy-donor enzyme and yellow fluorescent protein (YFP) as the energy-acceptor fluorophore, and obtained a clearly bimodal bioluminescence spectrum. Stable bioluminescence that is not influenced by environmental factors is highly desirable for reliable measurements in biological assays. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Sensitive detection of acrolein in serum using time-resolved luminescence

Togashi M., Urano Y., Kojima H., Terai T., Hanaoka K., Igarashi K., Hirata Y., Nagano T.

Organic Letters （Organic Letters） 12 （ 8 ） 1704 - 1707 2010年04月

研究論文（学術雑誌）, 査読有り, ISSN 15237060

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Development and application of a near-infrared fluorescence probe for oxidative stress based on differential reactivity of linked cyanine dyes

Oushiki D., Kojima H., Terai T., Arita M., Hanaoka K., Urano Y., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 132 （ 8 ） 2795 - 2801 2010年02月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

Reactive oxygen species (ROS) operate as signaling molecules under various physiological conditions, and overproduction of ROS is involved in the pathogenesis of many diseases. Therefore, fluorescent probes for visualizing ROS are promising tools with which to uncover the molecular mechanisms of physiological and pathological processes and might also be useful for diagnosis. Here we describe a novel fluorescence probe, FOSCY-1, operating in the physiologically favorable near-infrared region. The probe consists of two differentially ROS-reactive cyanine dyes connected by a linker; reaction of the more susceptible dye with ROS releases intramolecular fluorescence quenching of the less susceptible dye. We successfully applied this probe to detect ROS produced by HL60 cells and porcine neutrophils and for imaging oxidative stress in a mouse model of peritonitis. © 2010 American Chemical Society.

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花岡 健二郎

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花岡　健二郎

論文 - 花岡　健二郎