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ABSTRACT: Cancer cells evade replicative senescence by re-expressing telomerase, which maintains telomere length and hence chromosomal integrity. Telomerase inhibition would lead cancer cells to senesce and therefore prevent cancer cells from growing indefinitely. G-quadruplex ligands can attenuate telomerase activity by inducing G-quadruplex formation at the 3'-overhang of telomere and at the human telomerase reverse transcriptase (hTERT) promoter; the former prevents telomerase from accessing the telomere, and the latter acts as a transcriptional silencer. The present investigation found that perylene derivatives PM2 and PIPER induced G-quadruplex formation from both telomeric DNA and the hTERT promoter region in vitro. Further, TRAP assay showed that these compounds inhibited telomerase in a dose-dependent manner. When A549 human lung cancer cells were treated with these compounds, hTERT expression was down-regulated. Moreover, the crude protein extract from these treated cells exhibited less telomerase activity. In the long-term treatment of A549 lung cancer cells with sub-cytotoxic dose of these perylenes, telomere shortening, reduction of cell proliferation and tumorigenicity, and cell senescence were observed. The results of this study indicate that perylene derivatives warrant further consideration as effective agents for cancer therapy.
Bioorganic & medicinal chemistry 12/2012; · 2.82 Impact Factor
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ABSTRACT: The proximal promoter region of the human vascular endothelial growth factor (VEGF) gene contains a guanine-rich strand that can act as a transcriptional silencer by forming an intramolecular G-quadruplex. In this study, we compared two perylene monoimide derivatives, PM1 and PM2, with the well-studied perylene diimide derivative, PIPER, and the well-studied porphyrin derivative, TmPyP(4), with regard to G-quadruplex formation, G-quadruplex binding selectivity, and human VEGF gene silencing in A549 lung cancer cells. The results show that these perylene derivatives can preferentially induce intramolecular G-quadruplex formation from a duplex containing the VEGF G-quadruplex motif in vitro. Incubating A549 lung cancer cells with these perylene derivatives, especially PM2, led to the reduction of both VEGF mRNA and VEGF protein. This study might provide the foundation for the rational design and development of new perylene derivatives as effective anti-angiogenesis agents for cancer therapy.
Bioorganic & medicinal chemistry letters 11/2011; 22(1):518-22. · 2.65 Impact Factor
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ABSTRACT: The communication describes the synthesis and studies of 9-piperazine substituted perylene-3,4-dicarboximide (1). In aqueous solution, the ratio of fluorescence emission intensities from the localized excited state (∼585 nm) to the charge transfer excited state (∼695 nm) increases in the pH range of 7.5-9. Furthermore, compound 1 may be used for ratiometric detection of double-stranded DNA.
Chemical Communications 02/2011; 47(8):2291-3. · 6.17 Impact Factor
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ABSTRACT: In this manuscript, we report the fluorescence properties of N-(2-(N',N'-diethylamino)ethyl)perylene-3,4-dicarboximide (1) and its quaternized derivative N-(2-(N',N'- diethyl-N'-methylammonium)ethyl)perylene-3,4-dicarboximide tosylate (2) in organic solvents. The effects of carboxylic acids and amines on the fluorescence properties of these compounds were investigated. In addition, we studied the aggregation and fluorescence properties of (2) and its 9-bromo-substituted derivative (3) in aqueous solution. The fluorescent properties of these compounds change dramatically with the extent of aggregation, thus allowing these compounds to be used as fluorescent probes for changes in temperature and solvent polarity. For instance, the fluorescence emission intensity of 3 increases by about 28 times as the temperature of the solution increases from 10°C to 85°C. The fluorescent intensities of 2 and 3 in methanol are higher than that in water by about 8 and 25 times, respectively.
Journal of Fluorescence 01/2011; 21(1):213-22. · 2.11 Impact Factor
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ABSTRACT: We report a study of the chromonic liquid-crystalline properties of 2-(N,N-diethyl-N-methylammonium)ethylperylene-3,4-dicarboximide formate (1) in aqueous solution by polarised optical microscopy (POM), 2H nuclear magnetic resonance (NMR) spectroscopy and fluorescence spectroscopy. Compound 1 shows chromonic liquid-crystalline properties at concentrations higher than 4 wt% at room temperature. We showed that fluorescence spectroscopy could be used to determine the concentration-dependent, phase-transition temperatures of this chromonic liquid crystal. The values determined by fluorescence spectroscopy are consistent with the values determined by 2H NMR spectroscopy and POM.
Liquid Crystals 05/2010; 37(5):555-561. · 1.86 Impact Factor
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ABSTRACT: Atrial natriuretic peptide (ANP) plays a major role in blood pressure and volume regulation. ANP activities are mediated by a cell surface, single-span transmembrane receptor linked to its intrinsic guanylate cyclase activity. The crystal structures of the dimerized ANP receptor extracellular domain (ECD) with and without ANP have revealed a novel hormone-induced rotation mechanism occurring in the juxtamembrane region that appears to mediate signal transduction [Ogawa H, Qiu Y, Ogata CM & Misono KS (2004) J Biol Chem 279, 28625-28631]. However, the ECD crystal packing contains two major intermolecular contacts that suggest two possible dimer pairs: 'head-to-head' (hh) and 'tail-to-tail' (tt) dimers associated via the membrane-distal and membrane-proximal subdomains, respectively. The existence of these two potential dimer forms challenges the proposed signaling mechanism. In this study, we performed single-particle electron microscopy (EM) to determine the ECD dimer structures occurring in the absence of crystal contacts. EM reconstruction yielded the dimer structures with and without ANP in only the hh dimer forms. We further performed steady-state fluorescence spectroscopy of Trp residues, one of which (Trp74) occurs in the hh dimer interface and none of which occurs in the tt dimer interface. ANP binding caused a time-dependent decrease in Trp emission at 350 nm that was attributable to partially buried Trp74 in the unbound hh dimer interface becoming exposed to solvent water upon ANP binding. Thus, the results of single-particle EM and Trp fluorescence studies have provided direct evidence for hh dimer structures for unbound and ANP-bound receptor. The results also support the proposed rotation mechanism for transmembrane signaling by the ANP receptor.
FEBS Journal 01/2009; 276(5):1347-55. · 3.79 Impact Factor
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ABSTRACT: Chromonic liquid crystals (or chromonics) are formed by the self-organization of aromatic compounds with ionic or hydrophilic groups in aqueous solutions. This review summarizes the research on chromonic liquid crystals in the last two decades. The research embraced the studies of commercially available chromonic dyes and drugs, the syntheses and investigations of molecularly designed mesogens, the invention of novel processes for aligning chromonic liquid crystals, and the development of new applications as functional materials and biosensors.
Chemical Communications 06/2008; · 6.17 Impact Factor
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ABSTRACT: Ionic perylenebis(dicarboximide)s 1-5 were synthesized. The aggregation and liquid-crystalline properties of these compounds in aqueous solutions were investigated. In the concentration range of approximately 5 x 10-7-5 x 10-4 M, the structures of the ammonium side chains and counterions did not have a significant effect on the electronic transition properties and H-aggregate formation of these compounds. However, the liquid-crystalline phase properties varied with the structure of the side chains and the counterions. Ionic perylenebis(dicarboximide)s 1, 3, and 5 with chloride ions formed nematic (N) phases from the isotropic (I) phase, while 2 and 4 with p-methylbenzenesulfonate ions formed chromonic ribbons from the I phase. Studies by polarized light microscopy and 2H NMR spectroscopy indicated that the N phase of 5 (with gem dimethyl groups) formed at higher concentrations than those observed for 1 and 3 at the same temperature. Furthermore, the N phase of 5 was less ordered compared to those of 1 and 3 at a similar concentration and temperature, presumably due to the bulkiness of the side chains of 5 that hindered the stacking and pi-interactions of the aromatic rings.
Langmuir 04/2008; 24(5):2133-9. · 4.19 Impact Factor
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ABSTRACT: In this article, we present the design principles and application of a motif composed of a stem-loop probe (SP) hybridized to a fluorescently labeled universal reporter (UR) for sensing unlabeled nucleic acids. At room temperature, SP-UR is in the hairpin-closed form in which the fluorophore of UR is in proximity to the G bases of the hairpin, where consequently the fluorescent emission is quenched significantly. On hybridization with target, SP-UR is trapped in the hairpin-opened configuration in which the fluorophore and the G quenchers are apart. This turns off quenching, increases emission intensity, and signals the presence of target. Compared with the common approach that employs an oligonucleotide probe with a covalently linked fluorophore, the use of a fluorescently labeled universal reporter strand hybridized to an unlabeled stem-loop probe provides a more efficient approach to the fabrication of nucleic acid sensors and microarrays potentially useful for real-time analysis.
Analytical Biochemistry 08/2007; 366(2):126-30. · 3.00 Impact Factor
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ABSTRACT: In this communication, we report the self-organization of a perylenedicarboximide to produce materials that exhibit dichroic (direction-dependent) absorption and anisotropic fluorescence emission of visible light.
Chemical Communications 06/2007; · 6.17 Impact Factor
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ABSTRACT: We have developed an approach to generate micropatterns of anisotropic organic materials which exploits the self-organization, driven by pi-stacking and hydrophobic interactions, of an ionic perylenebis(dicarboximide) in aqueous solutions.
Chemical Communications 03/2006; · 6.17 Impact Factor
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ABSTRACT: The synthesis of an ionic quaterrylenebis(dicarboximide) 1a, a long-wavelength absorbing mesogen, is described. When compared with its analogue 2a, an ionic perylenebis(dicarboximide), the aromatic protons of 1a exchange with deuterium of concentrated D(2)SO(4) at a dramatically faster rate. In addition, stronger aggregation in aqueous media was observed for 1a.
The Journal of Organic Chemistry 05/2004; 69(8):2719-26. · 4.45 Impact Factor
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04/2004;
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ABSTRACT: The chromonic liquid-crystalline properties of bis-(N,N-diethylaminoethyl)perylene-3,4,9,10-tetracarboxylic diimide dihydrochloride in an aqueous solution were investigated by polarized light microscopy and 2H NMR spectroscopy. Both techniques indicate a narrow I + N biphasic region and a broad N phase region at concentrations ranging from approximately 6.9 to approximately 30 wt % at room temperature. Optical microscopy indicates that a hexagonal M phase exists at higher concentrations. The variation of the I --> N + I and N + I --> N transition temperatures with concentration was studied by 2H NMR spectroscopy. Finally, the effects of temperature and concentration on the order parameter of the N phase were investigated by 2H NMR using a tetra-deuterated derivative. A value of 0.97 was obtained for the N phase at its upper concentration limit.
Langmuir 02/2004; 20(2):342-7. · 4.19 Impact Factor
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05/2003;
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Angewandte Chemie International Edition 03/2003; 42(8):897-900. · 13.45 Impact Factor
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ABSTRACT: Cetyl myristoleate (CM) was reported by Diehl and May [J Pharm Sci 83 (1994) 296] to block inflammation and prevent adjuvant-induced arthritis in rats. To verify this earlier work, we have synthesized pure CM and tested its anti-arthritic properties in a collagen-induced arthritis model in DBA/1LacJ mice. Multiple intraperitoneal injections of CM in 450 and 900 mg kg(-1) doses resulted in a significantly lower incidence of disease and caused a modest but significant diminution in clinical signs in those mice that developed arthritis. CM administered in daily oral doses of 20 mg kg(-1) also reduced the incidence of arthritis and caused a small reduction in the clinical signs in mice that developed arthritis. Although the protective effect of CM in collagen-induced arthritis observed in the present study was less dramatic than that reported earlier, our results confirm the anti-arthritic properties of pure CM.
Pharmacological Research 02/2003; 47(1):43-7. · 4.44 Impact Factor
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ABSTRACT: We report the control of molecular orientation in solid films through self-organization and induced-orientation processes. We synthesized water-soluble cationic 3,4,9,10-perylene diimide (1) and studied its self-organization in aqueous solution. By UV−vis spectroscopy, H-aggregates of 1 were observed forming in solutions with concentrations as low as 10-7 M. At concentrations above approximately 0.1 M (7% w/w), these solutions were observed with polarized microscopy to form a chromonic N phase (a nematic lyotropic liquid crystalline phase) at room temperature. Upon induced alignment (by shearing) of the chromonic N phase on a glass substrate and removal of solvent, anisotropic solid films of the dichroic dye were produced. These films have dichroic ratio values that routinely exceed 25 and in some cases 30, making them excellent polarizers over the blue and green region. By use of a combination of polarized UV−vis and FT-IR spectroscopies, the orientation of the average molecular plane in these films was determined to be perpendicular to both the shearing direction and the substrate plane. Small-angle X-ray diffraction studies indicate that the molecules in the solid film possess a high degree of order.
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