26093-31-2Relevant articles and documents
HgII-selective fluorescent indicator: One-step synthesis
Kim, Seul-Bi,Cho, Dong-Gyu
, p. 2495 - 2498 (2012)
Fluorescent indicator 2 was synthesized by a single-step reaction. The indicator underwent an HgII-selective reaction (hydrolysis/ decarboxylation sequence) in the presence of HgII, which was verified by using LC-MS and NMR techniques.
Coumarin-coupled receptor as a membrane-permeable, Cu2+- selective fluorescent chemosensor for imaging copper(II) in HEPG-2 cell
Wang, Mao-Xiang,Huang, Sheng-Hai,Meng, Xiang-Ming,Zhu, Man-Zhou,Guo, Qing-Xiang
, p. 462 - 465 (2008)
A novel fluorescent chemosensor 1 for imaging labile Cu2+ in living biological samples was designed and synthesized; it exhibits very strong fluorescence responses to Cu2+, and its LSM images strongly support the existence of Cu2+ in HEGP-2 cell. Copyright
Organic azide inhibitors of cysteine proteases
Le, Giang Thanh,Abbenante, Giovanni,Madala, Praveen K.,Hoang, Huy N.,Fairlie, David P.
, p. 12396 - 12397 (2006)
Cysteine proteases are crucial regulatory enzymes in human physiology and disease. Inhibitors are usually designed with reactive electrophiles to covalently bond to the catalytic cysteinyl sulfur, and consequently they also indiscriminately interact with biological thiolates and other nucleophiles, leading to toxic side effects in vivo. Here we describe an alternative to using reactive electrophiles, demonstrating the use of a much less reactive azidomethylene substituent (-CH2-N3) that confers potent inhibition of cysteine proteases. This new approach resulted in potent, reversible, competitive inhibitors of caspase-1 (IC50 10 nM), with significant advantages over aldehydes such as high stability in vitro to thiols (10 mM dithiothreitol (pH 7.2), 20 mM glutathione (pH 7.2, 9, 11)) and aqueous media, as well as some highly desirable druglike features. It was also demonstrated that azides can be incorporated into inhibitors of other caspases (e.g. 3, 8) and cathepsins (e.g. K, S, B), indicating the versatility of this valuable new approach to cysteine protease inhibition. Copyright
A fluorescent assay suitable for inhibitor screening and vanin tissue quantification
Ruan, Benfang H.,Cole, Derek C.,Wu, Paul,Quazi, Amira,Page, Karen,Wright, Jill F.,Huang, Nelson,Stock, Joseph R.,Nocka, Karl,Aulabaugh, Ann,Krykbaev, Rustem,Fitz, Lori J.,Wolfman, Neil M.,Fleming, Margaret L.
, p. 284 - 292 (2010)
Vanin-1 is a pantetheinase that catalyzes the hydrolysis of pantetheine to produce pantothenic acid (vitamin B5) and cysteamine. Reported here is a highly sensitive fluorescent assay using a novel fluorescently labeled pantothenate derivative. The assay has been used for characterization of a soluble version of human vanin-1 recombinant protein, identification and characterization of hits from high-throughput screening (HTS), and quantification of vanin pantothenase activity in cell lines and tissues. Under optimized assay conditions, we quantified vanin pantothenase activity in tissue lysate and found low activity in lung and liver but high activity in kidney. We demonstrated that the purified recombinant vanin-1 consisting of the extracellular portion without the glycosylphosphatidylinositol (GPI) linker was highly active with an apparent Km of 28 μM for pantothenate-7-amino-4-methylcoumarin (pantothenate-AMC), which was converted to pantothenic acid and AMC based on liquid chromatography-mass spectrometry (LC-MS) analysis. The assay also performed well in a 384-well microplate format under initial rate conditions (10% conversion) with a signal-to-background ratio (S/B) of 7 and a Z factor of 0.75. Preliminary screening of a library of 1280 pharmaceutically active compounds identified inhibitors with novel chemical scaffolds. This assay will be a powerful tool for target validation and drug lead identification and characterization.
New ambipolar blue emitting materials based on amino coumarin derivatives with high efficiency for organic lightemitting diodes
Kim, Seungho,Lee, Kyung Jin,Kim, Beomjin,Lee, Jaehyun,Kay, Kwang-Yol,Park, Jongwook
, p. 8020 - 8024 (2013)
New blue emitting materials, 7-diphenylamino-4-methyl-coumarin (DPA-MC) and aminotri( 4-methylcoumarin) (T-MC) including coumarin moiety were synthesized by Ullman reaction. Optical and electronic properties were examined by UV-Vis. Absorption spectrum, PL spectrum, and cyclic voltammetry. UV-Vis. spectra of DPA-MC and T-MC in a film state showed maximum absorption wavelengths of 382 nm and 399 nm, respectively. PL spectra of DPA-MC and T-MC show maximum emission wavelengths of 463 nm and 481 nm respectively. Non-doped OLED devices were fabricated by using the synthesized materials as an emitting material layer. DPA-MC compound showed highly efficient luminescence properties. EL spectrum of DPA-MC exhibited a maximum value of 463 nm and DPA-MC device provided luminescence efficiency of 3.83 cd/A, power efficiency of 2.46 lm/W, external quantum efficiency of 3.71% and CIE coordinates of (0.154, 0.190) at a current density of 10 mA/cm2. In particular, Power efficiency increased by more than 1.6 times in DPA-MC (2.46 lm/W), which is higher than commercialized material, DPVBi (1.46 lm/W). High EL performance might come from ambipolar effects of a molecular structure. Copyright
In Vivo Two-Photon Fluorescence Imaging of the Activity of the Inflammatory Biomarker LTA4H in a Mouse Pneumonia Model
Wang, Hui,Xue, Ke,Li, Ping,Yang, Yuyun,He, Zixu,Zhang, Wei,Zhang, Wen,Tang, Bo
, p. 6020 - 6027 (2018)
Severe atmospheric haze caused by industrial pollution has severely affected human health and led to the increasing incidence of cardiopulmonary diseases, including pneumonia. Conventional methods for diagnosis of pneumonia are complicated and tedious, and current clinical imaging techniques might cause organ injuries to some extent. Therefore, an accurate, fast, and intact imaging method must be developed to diagnose pneumonia in the early stages. In this study, we propose a new two-photon fluorescence probe, named as ASPC, for detection of the activity of the inflammatory biomarker LTA4H through specific recognition and cleavage of amides containing the unnatural amino acid l-AspBzl. The activity of LTA4H in the lung tissues of mice was rapidly and accurately monitored for the first time and could be an indicator for diagnosis of pneumonia. The severity of pneumonia in mice caused by haze particulate was determined through imaging the activity of LTA4H as biomarker and confirmed using a commercial ELISA kit of interleukin-1β. This work provides a promising method for clinical detection of pneumonia and for screening specific depressors of LTA4H as potential drug candidates.
Purification and characterization of cathepsin L from the muscle of silver carp (Hypophthalmichthys molitrix)
Liu, Huan,Yin, Lijun,Zhang, Nan,Li, Shuhong,Ma, Changwei
, p. 9584 - 9591 (2006)
Cathepsin L in silver carp musle was purified to 48.4-fold by acid-heat treatment and ammonium sulfate fractionation, followed by a series of chromatographic separations. The molecular mass of the purified enzyme was 30 kDa determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme was activated by dithiothreitol and cysteine while it was substantially inhibited by E-64 and insensitive to PMSF and pepstatin A, suggesting that the purified enzyme belongs to a family of cysteine proteinase. Consistent with this conclusion, Zn2+, Cu2+, Co 2+, Ni2+, and Fe2+ could strongly inhibit the activity of this enzyme. The optimal pH and temperature were 5.0 and 55°C, respectively. The enzyme catalyzed the hydrolysis of Z-Phe-Arg-MCA with a parameter of Km (8.27 μM) and Kcat (28.7 s-1) but hardly hydrolyzed Z-Arg-Arg-MCA, Arg-MCA, and Boc-Val-Leu-Lys-MCA. The microstructure analysis by scanning electron microscopy showed that this proteinase is capable of destroying the network structure of silver carp surimi gels. The enzyme exhibited a higher hydrolytic activity on surimi protein at 65°C than at 40°C.
Effects of detergents on the West Nile virus protease activity
Ezgimen, Manolya D.,Mueller, Niklaus H.,Teramoto, Tadahisa,Padmanabhan
, p. 3278 - 3282 (2009)
Detergents such as Triton X-100 are often used in drug discovery research to weed out small molecule promiscuous and non-specific inhibitors which act by aggregation in solution and undesirable precipitation in aqueous assay buffers. We evaluated the effe
Microwave acceleration of the Pechmann reaction on graphite/montmorillonite K10: Application to the preparation of 4-substituted 7-aminocoumarins
Frère, Stéphane,Thiéry, Valérie,Besson, Thierry
, p. 2791 - 2794 (2001)
Efficient synthesis of 7-aminocoumarins was performed via the Pechmann reaction by microwave irradiation of the reactants on solid support (graphite/montmorillonite K10). In this convenient new methodology, the strong thermal effect due to graphite/microwaves interaction is associated with the acidic catalyst role of the clay.
Anti-AIDS agents 66: Syntheses and anti-HIV activity of phenolic and aza 3′,4′-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) derivatives
Suzuki, Madoka,Yu, Donglei,Morris-Natschke, Susan L.,Smith, Philip C.,Lee, Kuo-Hsiung
, p. 6852 - 6858 (2007)
New phenolic and aza 3′,4′-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogs were synthesized and assayed for inhibition of HIV-1 IIIB replication in H9 lymphocytes. Compound 16, 4-methyl-1′-aza-DCK (4-methyl-aza-DCK), was less lipophilic than 4-methyl-DCK, and retained sub-micromolar anti-HIV activity with EC50 and TI values of 0.77 μM and >42, respectively. Moreover, it showed moderately improved metabolic stability. Introduction of phenolic hydroxyl groups to 4-methyl-DCK decreased lipophilicity significantly, but did not improve metabolic stability and also decreased activity.
O,o-Difluorination of aromatic azide yields a fast-response fluorescent probe for H2S detection and for improved bioorthogonal reactions
Zhang, Jie,Gao, Yasi,Kang, Xueying,Zhu, Zhentao,Wang, Zhiqian,Xi, Zhen,Yi, Long
, p. 4212 - 4217 (2017)
The development of efficient bioorthogonal reactions for sensing of endogenous biomolecules and for bioconjugation should be of paramount importance in the field of chemical biology. In this work, the o,o′-difluorinated aromatic azide was firstly employed to develop a new fast-response fluorescent probe 1 for H2S detection and for bioorthogonal reactions. Compared with non- and mono-fluorinated probes, 1 showed faster reaction toward H2S, the third gasotransmitter, in buffer (pH 7.4), implying that the reaction rate could be enhanced by the dual-fluorine groups. Furthermore, such enhanced reaction rates of 1 were also observed in the Staudinger reaction and strain-promoted azide-alkyne cycloaddition (SPAAC) based on the comparison studies of the non-fluorinated probe. Our results firstly highlight that the o,o′-difluorinated aromatic azide group should be useful for fast bioorthogonal reactions and H2S detection.
Photochemical reactions of azidocoumarins.
Feng,Mahdavi-Anary,Partch,Li
, p. 813 - 817 (1995)
Photochemical reactions of 6-azidocoumarin and 7-azido-4-methylcoumarin in the presence of secondary amines have been investigated for their potential applications in photoaffinity labeling. It was found that the singlet nitrene generated from 6-azidocoumarin isomerized to a dehydroazepine intermediate that reacted with an amine to yield two isomeric adducts. Photolysis of 7-azido-4-methylcoumarin, in contrast, gave a triplet nitrene that abstracted hydrogen atoms from secondary amine molecules to form 7-amino-4-methylcoumarin as the major product. The difference in the intersystem crossing rate between the two compounds originates from the azido position relative to the carbonyl group. Because of its ability to form a covalent linkage with a nucleophile, 6-azidocoumarin is deemed to have a greater potential as a photoaffinity label than 7-azido-4-methylcoumarin.
Low molecular weight trypsin from hepatopancreas of freshwater prawn (Macrobrachium rosenbergii): Characteristics and biochemical properties
Sriket, Chodsana,Benjakul, Soottawat,Visessanguan, Wonnop,Hara, Kenji,Yoshida, Asami,Liang, Xiao
, p. 351 - 358 (2012)
Trypsin was purified to homogeneity from hepatopancreas of freshwater prawn (HFWP) (Macrobrachium rosenbergii) using a series of chromatographies including Q-Sepharose, Superdex 75 and MonoQ columns. HFWP trypsin was purified 525-fold with a yield of 10.6%. Based on native-PAGE, the purified trypsin showed a single band. Trypsin had a molecular weight of 17 kDa as estimated by SDS-PAGE. The optimal pH and temperature for Boc-Val-Pro-Arg-MCA hydrolysis were 8.0 and 55 °C, respectively. Trypsin was stable to heat treatment up to 40 °C, and over a pH range of 7.0-11.0. Trypsin activity was strongly inhibited by soybean trypsin inhibitor, N-p-tosyl-L-lysine chloromethyl ketone (TLCK) and Pefabloc SC and was partially inhibited by ethylenediaminetetraacetic acid (EDTA). Apparent Km value of trypsin was 0.24 μM and K cat value was 607.56 s-1 for Boc-Val-Pro-Arg-MCA. The N-terminal amino acid sequence of 20 residues of HFWP trypsin was IVGGDEAAPGEFPHQISMQV, which was highly homologous with those from other species of prawn. HFWP trypsin also showed high collagenolytic activity toward prawn, shrimp and fish collagens, suggesting its possible role in muscle softening of freshwater prawn during extended storage.
Hydrolysis of dipeptide derivatives reveals the diversity in the M49 family
Jajcanin-Jozic, Nina,Abramic, Marija
, p. 767 - 771 (2013)
Dipeptidyl peptidase III, a metallopeptidase of the M49 family, was first identified (in the pituitary) by its specific cleavage of diarginyl arylamides, which have been used as preferred assay substrates until now. Here we examined the activity of the yeast and human dipeptidyl peptidase III in parallel. The human enzyme preferred Arg2-β-naphthylamide and showed 620-fold higher kcat/Km for this substrate. In contrast, the yeast enzyme did not display a preference for any of the X-Arg-β-naphthylamide analyzed. The replacement of Gly505 with Asp, resulted in a less active, but more selective, yeast enzyme form. These results indicate diversity in cleavage specificity in the M49 family.
Masked Amino Trimethyl Lock (H2N-TML) Systems: New Molecular Entities for the Development of Turn-On Fluorophores and Their Application in Hydrogen Sulfide (H2S) Imaging in Human Cells
Jimidar, Claire Cheyenne,Grunenberg, J?rg,Karge, Bianka,Fuchs, Hazel Leanne Sarah,Br?nstrup, Mark,Klahn, Philipp
supporting information, (2021/11/10)
Masked trimethyl lock (TML) systems as molecular moieties enabling the bioresponsive release of compounds or dyes in a controlled temporal and spatial manner have been widely applied for the development of drug conjugates, prodrugs or molecular imaging tools. Herein, we report the development of a novel amino trimethyl lock (H2N-TML) system as an auto-immolative molecular entity for the release of fluorophores. We designed Cou-TML-N3 and MURh-TML-N3, two azide-masked turn-on fluorophores. The latter was demonstrated to selectively release fluorescent MURh in the presence of physiological concentrations of the redox-signaling molecule H2S in vitro and was successfully applied to image H2S in human cells.
Generation of H2S from Thiol-Dependent NO Reactivity of Model [4Fe-4S] Cluster and Roussin's Black Anion
Oakley, Kady M.,Zhao, Ziyi,Lehane, Ryan L.,Ma, Ji,Kim, Eunsuk
, p. 15910 - 15917 (2021/07/20)
Iron-sulfur clusters (Fe-S) have been well established as a target for nitric oxide (NO) in biological systems. Complementary to protein-bound studies, synthetic models have provided a platform to study what iron nitrosylated products and byproducts are produced depending on a controlled reaction environment. We have previously shown a model [2Fe-2S] system that produced a dinitrosyl iron complex (DNIC) upon nitrosylation along with hydrogen sulfide (H2S), another important gasotransmitter, in the presence of thiol, and hypothesized a similar reactivity pattern with [4Fe-4S] clusters which have largely produced inconsistent reaction products across biological and synthetic systems. Roussin's black anion (RBA), [Fe4(μ3-S)3(NO)7]-, is a previously established reaction product from synthetic [4Fe-4S] clusters with NO. Here, we present a new reactivity for the nitrosylation of a synthetic [4Fe-4S] cluster in the presence of thiol and thiolate. [Et4N]2[Fe4S4(SPh)4] (1) was nitrosylated in the presence of excess PhSH to generate H2S and an "RBA-like"intermediate that when further reacted with [NEt4][SPh] produced a {Fe(NO)2}9 DNIC, [Et4N][Fe(NO)2(SPh)2] (2). This "RBA-like"intermediate proved difficult to isolate but shares striking similarities to RBA in the presence of thiol based on IR υ(NO) stretching frequencies. Surprisingly, the same reaction products were produced when the reaction started with RBA and thiol. Similar to 1/NO, RBA in the presence of thiol and thiolate generates stoichiometric amounts of DNIC while releasing its bridging sulfides as H2S. These results suggest not only that RBA may not be the final product of [4Fe-4S] + NO but also that RBA has unprecedented reactivity with thiols and thiolates which may explain current challenges around identifying biological nitrosylated Fe-S clusters.
Coumarins by Direct Annulation: β-Borylacrylates as Ambiphilic C3-Synthons
Wienhold, Max,Molloy, John J.,Daniliuc, Constantin G.,Gilmour, Ryan
, p. 685 - 689 (2020/11/30)
Modular β-borylacrylates have been validated as programmable, ambiphilic C3-synthons in the cascade annulation of 2-halo-phenol derivatives to generate structurally and electronically diverse coumarins. Key to this [3+3] disconnection is the BPin unit which serves a dual purpose as both a traceless linker for C(sp2)–C(sp2) coupling, and as a chromophore extension to enable inversion of the alkene geometry via selective energy transfer catalysis. Mild isomerisation is a pre-condition to access 3-substituted coumarins and provides a handle for divergence. The method is showcased in the synthesis of representative natural products that contain this venerable chemotype. Facile entry into π-expanded estrone derivatives modified at the A-ring is disclosed to demonstrate the potential of the method in bioassay development or in drug repurposing.
