研究者詳細 - 花岡　健二郎

論文 - 花岡　健二郎

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Selective ablation of β-galactosidase-expressing cells with a rationally designed activatable photosensitizer

Ichikawa Y., Kamiya M., Obata F., Miura M., Terai T., Komatsu T., Ueno T., Hanaoka K., Nagano T., Urano Y.

Angewandte Chemie - International Edition （Angewandte Chemie - International Edition） 53 （ 26 ） 6772 - 6775 2014年06月

研究論文（学術雑誌）, 査読有り, ISSN 14337851

We have developed an activatable photosensitizer capable of specifically inducing the death of β-galactosidase-expressing cells in response to photoirradiation. By using a selenium-substituted rhodol scaffold bearing β-galactoside as a targeting substituent, we designed and synthesized HMDESeR-βGal, which has a non-phototoxic spirocyclic structure owing to the presence of the galactoside moiety. However, β-galactosidase efficiently converted HMDESeR-βGal into phototoxic HMDESeR, which exists predominantly in the open xanthene form. This structural change resulted in drastic recovery of visible-wavelength absorption and the ability to generate singlet oxygen (1O2). When HMDESeR-βGal was applied to larval Drosophila melanogaster wing disks, which express β-galactosidase only in the posterior region, photoirradiation induced cell death in the β-galactosidase-expressing region with high specificity. Bull's eye! An activatable photosensitizer capable of specifically inducing the death of β-galactosidase-expressing cells in response to light irradiation was developed. Reaction with the enzyme resulted in a dynamic structural change to the phototoxic open form (see scheme), thus enabling the specific ablation of cells of interest in living tissues. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Primary hepatocytes from mice lacking cysteine dioxygenase show increased cysteine concentrations and higher rates of metabolism of cysteine to hydrogen sulfide and thiosulfate

Jurkowska H., Roman H., Hirschberger L., Sasakura K., Nagano T., Hanaoka K., Krijt J., Stipanuk M.

Amino Acids （Amino Acids） 46 （ 5 ） 1353 - 1365 2014年05月

研究論文（学術雑誌）, 査読有り, ISSN 09394451

The oxidation of cysteine in mammalian cells occurs by two routes: a highly regulated direct oxidation pathway in which the first step is catalyzed by cysteine dioxygenase (CDO) and by desulfhydration-oxidation pathways in which the sulfur is released in a reduced oxidation state. To assess the effect of a lack of CDO on production of hydrogen sulfide (H2S) and thiosulfate (an intermediate in the oxidation of H2S to sulfate) and to explore the roles of both cystathionine γ-lyase (CTH) and cystathionine β-synthase (CBS) in cysteine desulfhydration by liver, we investigated the metabolism of cysteine in hepatocytes isolated from Cdo1-null and wild-type mice. Hepatocytes from Cdo1-null mice produced more H2S and thiosulfate than did hepatocytes from wild-type mice. The greater flux of cysteine through the cysteine desulfhydration reactions catalyzed by CTH and CBS in hepatocytes from Cdo1-null mice appeared to be the consequence of their higher cysteine levels, which were due to the lack of CDO and hence lack of catabolism of cysteine by the cysteinesulfinate-dependent pathways. Both CBS and CTH appeared to contribute substantially to cysteine desulfhydration, with estimates of 56 % by CBS and 44 % by CTH in hepatocytes from wild-type mice, and 63 % by CBS and 37 % by CTH in hepatocytes from Cdo1-null mice. © 2014 Springer-Verlag Wien.

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Unbalanced excitability underlies offline reactivation of behaviorally activated neurons

Mizunuma M., Norimoto H., Tao K., Egawa T., Hanaoka K., Sakaguchi T., Hioki H., Kaneko T., Yamaguchi S., Nagano T., Matsuki N., Ikegaya Y.

Nature Neuroscience （Nature Neuroscience） 17 （ 4 ） 503 - 505 2014年04月

研究論文（学術雑誌）, 査読有り, ISSN 10976256

Hippocampal sharp waves (SWs)/ripples represent the reactivation of neurons involved in recently acquired memory and are crucial for memory consolidation. By labeling active cells with fluorescent protein under the control of an immediate-early gene promoter, we found that neurons that had been activated while mice explored a novel environment were preferentially reactivated during spontaneous SWs in hippocampal slices in vitro. During SWs, the reactivated neurons received strong excitatory synaptic inputs as opposed to a globally tuned network balance between excitation and inhibition. © 2014 Nature America, Inc. All rights reserved.

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Covalent attachment of mechanoresponsive luminescent micelles to glasses and polymers in aqueous conditions

Sagara Y., Komatsu T., Ueno T., Hanaoka K., Kato T., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 136 （ 11 ） 4273 - 4280 2014年03月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

Covalent attachment of mechanoresponsive luminescent organic or organometallic compounds to other materials is a promising approach to develop a wide variety of mechanoresponsive luminescent materials. Here, we report covalently linkable mechanoresponsive micelles that change their photoluminescence from yellow to green in response to mechanical stimulation under aqueous conditions. These micelles are composed of a dumbbell-shaped amphiphilic pyrene derivative having amine groups at the peripheral positions of its dendrons. Using a well-established cross-linker, the micelles were covalently linked via their peripheral amine groups to the surface of glass beads, polylactic acid (PLA) beads, and living cells under aqueous conditions. Vortexing of glass beads bearing the micelles in a glass vial filled with water caused a photoluminescence color change from yellow to green. PLA beads bearing the micelles showed no change in photoluminescence color under the same conditions. We ascribe this result to the lower density and stiffness of the PLA beads, because the color of the PLA beads changed on vortexing in the presence of bare glass beads. HeLa cells and HL-60 cells bearing the micelles showed no obvious photoluminescence color change under vortexing. The structure, photophysical properties, and mechanism of photoluminescence color change of the micellar assemblies were examined. © 2014 American Chemical Society.

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Development of azo-based fluorescent probes to detect different levels of hypoxia

Piao W., Tsuda S., Tanaka Y., Maeda S., Liu F., Takahashi S., Kushida Y., Komatsu T., Ueno T., Terai T., Nakazawa T., Uchiyama M., Morokuma K., Nagano T., Hanaoka K.

Angewandte Chemie - International Edition （Angewandte Chemie - International Edition） 52 （ 49 ） 13028 - 13032 2013年12月

研究論文（学術雑誌）, 査読有り, ISSN 14337851

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A water-soluble mechanochromic luminescent pyrene derivative exhibiting recovery of the initial photoluminescence color in a high-humidity environment

Sagara Y., Komatsu T., Ueno T., Hanaoka K., Kato T., Nagano T.

Advanced Functional Materials （Advanced Functional Materials） 23 （ 42 ） 5277 - 5284 2013年11月

研究論文（学術雑誌）, 査読有り, ISSN 1616301X

Switching of the luminescence properties of molecular materials in response to mechanical stimulation is of fundamental interest and also has a range of potential applications. Herein, a water-soluble mechanochromic luminescent pyrene derivative having two hydrophilic dendrons is reported. This pyrene derivative is the first example of a mechanochromic luminescent organic compound that responds to relative humidity. Mechanical stimulation (grinding) of this pyrene derivative in the solid state results in a change of the photoluminescence from yellow to green. Subsequent exposure to water vapor induces recovery of the initial yellow photoluminescence. The color change is reversible through at least ten cycles. It is also demonstrated that this compound can be applied as a mechano-sensing material in frictional wear testing for grease, owing to its immiscibility in non-polar solvents and its non-crystalline behavior. Transmission electron microscope and atomic force microscope observations of samples prepared from dilute aqueous solutions of the pyrene derivative on suitable substrates, together with dynamic light scattering measurements for the compound in aqueous solution, indicate that this amphiphilic dumbbell-shaped molecule forms micelles in water. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Diced electrophoresis gel assay for screening enzymes with specified activities

Komatsu T., Hanaoka K., Adibekian A., Yoshioka K., Terai T., Ueno T., Kawaguchi M., Cravatt B., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 135 （ 16 ） 6002 - 6005 2013年04月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

We have established the diced electrophoresis gel (DEG) assay as a proteome-wide screening tool to identify enzymes with activities of interest using turnover-based fluorescent substrates. The method utilizes the combination of native polyacrylamide gel electrophoresis (PAGE) with a multiwell-plate- based fluorometric assay to find protein spots with the specified activity. By developing fluorescent substrates that mimic the structure of neutrophil chemoattractants, we could identify enzymes involved in metabolic inactivation of the chemoattractants. © 2013 American Chemical Society.

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Red fluorescent probe for monitoring the dynamics of cytoplasmic calcium ions

Egawa T., Hirabayashi K., Koide Y., Kobayashi C., Takahashi N., Mineno T., Terai T., Ueno T., Komatsu T., Ikegaya Y., Matsuki N., Nagano T., Hanaoka K.

Angewandte Chemie - International Edition （Angewandte Chemie - International Edition） 52 （ 14 ） 3874 - 3877 2013年04月

研究論文（学術雑誌）, 査読有り, ISSN 14337851

We see red (and yellow and green): Probe 1 was developed for the visualization of cytoplasmic Ca2+, a pivotal second messenger in many biological responses. The new probe is suitable for multicolor imaging for the simultaneous detection of metal ions or proteins and is superior to the existing red fluorescent probe Rhod-2 for the monitoring of cytoplasmic Ca2+ oscillation in cultured cells (see fluorescence images of cells with 1 (top) and Rhod-2 (bottom)). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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TokyoGreen derivatives as specific and practical fluorescent probes for UDP-glucuronosyltransferase (UGT) 1A1

Terai T., Tomiyasu R., Ota T., Ueno T., Komatsu T., Hanaoka K., Urano Y., Nagano T.

Chemical Communications （Chemical Communications） 49 （ 30 ） 3101 - 3103 2013年03月

研究論文（学術雑誌）, 査読有り, ISSN 13597345

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Rational design of highly sensitive fluorescence probes for protease and glycosidase based on precisely controlled spirocyclization

Sakabe M., Asanuma D., Kamiya M., Iwatate R.J., Hanaoka K., Terai T., Nagano T., Urano Y.

Journal of the American Chemical Society （Journal of the American Chemical Society） 135 （ 1 ） 409 - 414 2013年01月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

We have synthesized and evaluated a series of hydroxymethyl rhodamine derivatives and found an intriguing difference of intramolecular spirocyclization behavior: the acetylated derivative of hydroxymethyl rhodamine green (Ac-HMRG) exists as a closed spirocyclic structure in aqueous solution at physiological pH, whereas HMRG itself takes an open nonspirocyclic structure. Ac-HMRG is colorless and nonfluorescent, whereas HMRG is strongly fluorescent. On the basis of these findings, we have developed a general design strategy to obtain highly sensitive fluorescence probes for proteases and glycosidases, by replacing the acetyl group of Ac-HMRG with a substrate moiety of the target enzyme. Specific cleavage of the substrate moiety in the nonfluorescent probe by the target enzyme generates a strong fluorescence signal. To confirm the validity and flexibility of our strategy, we designed and synthesized fluorescence probes for leucine aminopeptidase (Leu-HMRG), fibroblast activation protein (Ac-GlyPro-HMRG), and β-galactosidase (βGal-HMRG). All of these probes were almost nonfluorescent due to the formation of spirocyclic structure, but were converted efficiently to highly fluorescent HMRG by the target enzymes. We confirmed that the probes can be used in living cells. These probes offer great practical advantages, including high sensitivity and rapid response (due to regulation of fluorescence at a single reactive site), as well as resistance to photobleaching, and are expected to be useful for a range of biological and pathological investigations. © 2012 American Chemical Society.

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Reversible off-on fluorescence probe for hypoxia and imaging of hypoxia-normoxia cycles in live cells

Takahashi S., Piao W., Matsumura Y., Komatsu T., Ueno T., Terai T., Kamachi T., Kohno M., Nagano T., Hanaoka K.

Journal of the American Chemical Society （Journal of the American Chemical Society） 134 （ 48 ） 19588 - 19591 2012年12月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

We report a fully reversible off-on fluorescence probe for hypoxia. The design employs QSY-21 as a Förster resonance energy transfer (FRET) acceptor and cyanine dye Cy5 as a FRET donor, based on our finding that QSY-21 undergoes one-electron bioreduction to the radical under hypoxia, with an absorbance decrease at 660 nm. At that point, FRET can no longer occur, and the dye becomes strongly fluorescent. Upon recovery of normoxia, the radical is immediately reoxidized to QSY-21, with loss of fluorescence due to restoration of FRET. We show that this probe, RHyCy5, can monitor repeated hypoxia-normoxia cycles in live cells. © 2012 American Chemical Society.

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Design strategy for a near-infrared fluorescence probe for matrix metalloproteinase utilizing highly cell permeable boron dipyrromethene

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

Journal of the American Chemical Society （Journal of the American Chemical Society） 134 （ 33 ） 13730 - 13737 2012年08月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

Near-infrared (NIR) fluorescence probes are especially useful for simple and noninvasive in vivo imaging inside the body because of low autofluorescence and high tissue transparency in the NIR region compared with other wavelength regions. However, existing NIR fluorescence probes for matrix metalloproteinases (MMPs), which are tumor, atherosclerosis, and inflammation markers, have various disadvantages, especially as regards sensitivity. Here, we report a novel design strategy to obtain a NIR fluorescence probe that is rapidly internalized by free diffusion and well retained intracellularly after activation by extracellular MMPs. We designed and synthesized four candidate probes, each consisting of a cell permeable or nonpermeable NIR fluorescent dye as a Förster resonance energy transfer (FRET) donor linked to the NIR dark quencher BHQ-3 as a FRET acceptor via a MMP substrate peptide. We applied these probes for detection of the MMP activity of cultured HT-1080 cells, which express MMP2 and MT1-MMP, by fluorescence microscopy. Among them, the probe incorporating BODIPY650/665, BODIPY-MMP, clearly visualized the MMP activity as an increment of fluorescence inside the cells. We then applied this probe to a mouse xenograft tumor model prepared with HT-1080 cells. Following intratumoral injection of the probe, MMP activity could be visualized for much longer with BODIPY-MMP than with the probe containing SulfoCy5, which is cell impermeable and consequently readily washed out of the tissue. This simple design strategy should be applicable to develop a range of sensitive, rapidly responsive NIR fluorescence probes not only for MMP activity, but also for other proteases. © 2012 American Chemical Society.

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Highly activatable and environment-insensitive optical highlighters for selective spatiotemporal imaging of target proteins

Kobayashi T., Komatsu T., Kamiya M., Campos C., González-Gaitán M., Terai T., Hanaoka K., Nagano T., Urano Y.

Journal of the American Chemical Society （Journal of the American Chemical Society） 134 （ 27 ） 11153 - 11160 2012年07月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

Optical highlighters are photoactivatable fluorescent molecules that exhibit pronounced changes in their spectral properties in response to irradiation with light of a specific wavelength and intensity. Here, we present a novel design strategy for a new class of caged BODIPY (4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene) fluorophores, based on the use of photoremovable protecting groups (PRPGs) with high reduction potentials that serve as both a photosensitive unit and a fluorescence quencher via photoinduced electron transfer (PeT). 2,6-Dinitrobenzyl (DNB)-caged BODIPY was efficiently photoactivated, with activation ratios exceeding 600-fold in aqueous solutions. We then combined this photoactivatable fluorophore with a SNAP (mutant of O 6-alkylguanine DNA alkyltransferase) ligand to obtain a small-molecule-based optical highlighter for visualization of protein dynamics, using the well-established SNAP tag technology. As proof of concept, we demonstrate spatiotemporal imaging of the fusion protein of epidermal growth factor receptor (EGFR) with SNAP tag in living cells. We also demonstrate highlighting of cells of interest in live zebrafish embryos, using the fusion protein of histone 2A with SNAP tag. © 2012 American Chemical Society.

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Red fluorescent scaffold for highly sensitive protease activity probes

Kushida Y., Hanaoka K., Komatsu T., Terai T., Ueno T., Yoshida K., Uchiyama M., Nagano T.

Bioorganic and Medicinal Chemistry Letters （Bioorganic and Medicinal Chemistry Letters） 22 （ 12 ） 3908 - 3911 2012年06月

研究論文（学術雑誌）, 査読有り, ISSN 0960894X

We have developed a novel red fluorescent dye, 2Me SiR600 (λem = 613 nm), in which the O atom of Rhodamine Green at the 10 position of the xanthene moiety is replaced with a Si atom, as a scaffold for probes to detect protease activity with extremely high S/N ratio. As proof of concept, we designed and synthesized probes for caspase-3 activity (Z-DEVD-SiR600) and leucine aminopeptidase activity (Leu-SiR600). Caspase-3-mediated cleavage of Z-DEVD-SiR600 resulted in a large bathochromic shift (93 nm) of the absorption maximum and a 432-fold fluorescence enhancement. © 2012 Elsevier Ltd. All rights reserved.

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Near-infrared fluorescence probes for enzymes based on binding affinity modulation of squarylium dye scaffold

Oushiki D., Kojima H., Takahashi Y., Komatsu T., Terai T., Hanaoka K., Nishikawa M., Takakura Y., Nagano T.

Analytical Chemistry （Analytical Chemistry） 84 （ 10 ） 4404 - 4410 2012年05月

研究論文（学術雑誌）, 査読有り, ISSN 00032700

We present a novel design strategy for near-infrared (NIR) fluorescence probes utilizing dye-protein interaction as a trigger for fluorescence enhancement. The design principle involves modification of a polymethine dye with cleavable functional groups that reduce the dye's protein-binding affinity. When these functional groups are removed by specific interaction with the target enzymes, the dye's protein affinity is restored, protein binding occurs, and the dye's fluorescence is strongly enhanced. To validate this strategy, we first designed and synthesized an alkaline phosphatase (ALP) sensor by introducing phosphate into the squarylium dye scaffold; this sensor was able to detect ALP-labeled secondary antibodies in Western blotting analysis. Second, we synthesized a probe for β-galactosidase (widely used as a reporter of gene expression) by means of β-galactosyl substitution of the squarylium scaffold; this sensor was able to visualize β-galactosidase activity both in vitro and in vivo. Our strategy should be applicable to obtain NIR fluorescence probes for a wide range of target enzymes. © 2012 American Chemical Society.

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Development of hypoxia-sensitive Gd <sup>3+</sup>-based MRI contrast agents

Iwaki S., Hanaoka K., Piao W., Komatsu T., Ueno T., Terai T., Nagano T.

Bioorganic and Medicinal Chemistry Letters （Bioorganic and Medicinal Chemistry Letters） 22 （ 8 ） 2798 - 2802 2012年04月

研究論文（学術雑誌）, 査読有り, ISSN 0960894X

Hypoxia occurs in various diseases, including cancer, ischemia, and acute and chronic vascular diseases. Here we describe the design and synthesis of the first hypoxia-sensitive MRI contrast agents, SAGds. SAGds showed a pH-dependent r 1 relaxivity change associated with intramolecular chelation of the nitrogen atom of the sulfonamide moiety to the Gd 3+ center. There was a correlation between the pK a of the r 1 relaxivity change and the sum of the Hammett σ constants of substituents on the aromatic ring. Among the synthesized compounds, 4NO 22MeOSAGd was selectively reduced to the amine by rat liver microsomes under hypoxic conditions, resulting in a 1.8-fold increment of the r 1 relaxivity owing to the change in pK a of the arylsulfonamide moiety. This enhancement of the r 1 relaxivity could be clearly detected in T 1-weighted MR images. Thus, 4NO 22MeOSAGd is a 'smart' MRI contrast agent for the detection of hypoxia under physiological conditions. © 2012 Elsevier Ltd. All rights reserved.

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Development of NIR fluorescent dyes based on Si-rhodamine for in vivo imaging

Koide Y., Urano Y., Hanaoka K., Piao W., Kusakabe M., Saito N., Terai T., Okabe T., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 134 （ 11 ） 5029 - 5031 2012年03月

研究論文（学術雑誌）, ISSN 00027863

We have developed a series of novel near-infrared (NIR) wavelength-excitable fluorescent dyes, SiR-NIRs, by modifying the Si-rhodamine scaffold to obtain emission in the range suitable for in vivo imaging. Among them, SiR680 and SiR700 showed sufficiently high quantum efficiency in aqueous media. Both antibody-bound and free dye exhibited high tolerance to photobleaching in aqueous solution. Subcutaneous xenograft tumors were successfully visualized in a mouse tumor model using SiR700-labeled anti-tenascin-C (TN-C) antibody, SiR700-RCB1. SiR-NIRs are expected to be useful as labeling agents for in vivo imaging studies including multicolor imaging, and also as scaffolds for NIR fluorescence probes. © 2012 American Chemical Society.

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A reversible near-infrared fluorescence probe for reactive oxygen species based on Te-rhodamine

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

Chemical Communications （Chemical Communications） 48 （ 25 ） 3091 - 3093 2012年02月

研究論文（学術雑誌）, 査読有り, ISSN 13597345

We have designed and synthesized a reversible near-infrared (NIR) fluorescence probe, 2-Me TeR, for reactive oxygen species (ROS), utilizing the redox properties of the tellurium (Te) atom. 2-Me TeR is oxidized to fluorescent 2-Me TeOR by various ROS, while the generated 2-Me TeOR is quickly reduced in the presence of glutathione to regenerate 2-Me TeR. This redox-induced reversible NIR-fluorescence response of 2-Me TeR allowed us to detect the endogenous production of ROS and subsequent homeostatic recovery of the intracellular reductive environment in hydrogen peroxide-stimulated HL-60 cells. This probe is expected to be useful for monitoring the dynamics of ROS production continuously in vivo © 2012 Royal Society of Chemistry.

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Selective two-step labeling of proteins with an off/on fluorescent probe

Hirabayashi K., Hanaoka K., Shimonishi M., Terai T., Komatsu T., Ueno T., Nagano T.

Chemistry - A European Journal （Chemistry - A European Journal） 17 （ 52 ） 14763 - 14771 2011年12月

研究論文（学術雑誌）, 査読有り, ISSN 09476539

We present a novel design strategy for off/on fluorescent probes suitable for selective two-step labeling of proteins. To validate this strategy, we designed and synthesized an off/on fluorescent probe, 1-Ni 2+, which targets a cysteine-modified hexahistidine (His) tag. The probe consists of dichlorofluorescein conjugated with nitrilotriacetic acid (NTA)-Ni 2+ as the His-tag recognition site and a 2,4-dinitrophenyl ether moiety, which quenches the probe's fluorescence by photoinduced electron transfer (PeT) from the excited fluorophore to the 2,4-dinitrophenyl ether (donor-excited PeT; d-PeT) and also has reactivity with cysteine. His-tag recognition by the NTA-Ni 2+ moiety is followed by removal of the 2,4-dinitrophenyl ether quencher by proximity-enhanced reaction with the cysteine residue of the modified tag; this results in a marked fluorescence increase. Addition of His-tag peptide bearing a cysteine residue to aqueous probe solution resulted in about 20-fold fluorescence increment within 10 min, which is the largest fluorescence enhancement so far obtained with a visible light-excitable fluorescent probe for a His-based peptide tag. Further, we successfully visualized CysHis 6-peptide tethered to microbeads without any washing step. The probe also showed a large fluorescence increment in the presence of His 6Cys-tagged enhanced blue fluorescent protein (EBFP), but not His 6-tagged EBFP. We consider this system is superior to large fluorescence tags (e.g., green fluorescent protein: 27 kDa), which can perturb protein folding, trafficking and function, and also to existing small tags, which generally show little fluorescence increase upon target recognition and therefore require a washout step. This strategy should also be applicable to other tags. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Development of a highly selective fluorescence probe for hydrogen sulfide

Sasakura K., Hanaoka K., Shibuya N., Mikami Y., Kimura Y., Komatsu T., Ueno T., Terai T., Kimura H., Nagano T.

Journal of the American Chemical Society （Journal of the American Chemical Society） 133 （ 45 ） 18003 - 18005 2011年11月

研究論文（学術雑誌）, 査読有り, ISSN 00027863

Hydrogen sulfide (H 2S) has recently been identified as a biological response modifier. Here, we report the design and synthesis of a novel fluorescence probe for H 2S, HSip-1, utilizing azamacrocyclic copper(II) ion complex chemistry to control the fluorescence. HSip-1 showed high selectivity and high sensitivity for H 2S, and its potential for biological applications was confirmed by employing it for fluorescence imaging of H 2S in live cells. © 2011 American Chemical Society.

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花岡 健二郎

論文 - 花岡 健二郎

花岡　健二郎

論文 - 花岡　健二郎