A Fluorescent Carbazole Derivative:  High Sensitivity for Quadruplex DNA

Chang, Cheng-Chung; Wu, Jinyi; Chien, Chih‐Wei; Wu, Wei-Sung; Liu, Heng; Kang, Chi-Chih; Yu, L. J.; Chang, Ta‐Chau

doi:10.1021/ac034789i

Cited by 130 publications

(87 citation statements)

References 29 publications

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“…There is evidence to suggest that G-quadruplexes exist in vivo, and it is believed that these structures act as signaling elements (22)(23)(24); however, direct evidence for the formation of these structures in vivo is still emerging. For example, the identification of antibodies and proteins that preferentially bind to, stabilize, unwind, or cleave G-quadruplexes provides evidence for their existence in vivo (25,26).…”

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confidence: 99%

Identification and Characterization of Nucleolin as a c-myc G-quadruplex-binding Protein

González¹,

Guo

Hurley³

et al. 2009

Journal of Biological Chemistry

281

329

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myc is a proto-oncogene that plays an important role in the promotion of cellular growth and proliferation. Understanding the regulation of c-myc is important in cancer biology, as it is overexpressed in a wide variety of human cancers, including most gynecological, breast, and colon cancers. We previously demonstrated that a guanine-rich region upstream of the P1 promoter of c-myc that controls 85-90% of the transcriptional activation of this gene can form an intramolecular G-quadruplex (G4) that functions as a transcriptional repressor element. In this study, we used an affinity column to purify proteins that selectively bind to the human c-myc G-quadruplex. We found that nucleolin, a multifunctional phosphoprotein, binds in vitro to the c-myc G-quadruplex structure with high affinity and selectivity when compared with other known quadruplex structures. In addition, we demonstrate that upon binding, nucleolin facilitates the formation and increases the stability of the c-myc G-quadruplex structure. Furthermore, we provide evidence that nucleolin overexpression reduces the activity of a c-myc promoter in plasmid presumably by inducing and stabilizing the formation of the c-myc G-quadruplex. Finally, we show that nucleolin binds to the c-myc promoter in HeLa cells, which indicates that this interaction occurs in vivo. In summary, nucleolin may induce c-myc G4 formation in vivo.

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confidence: 99%

Identification and Characterization of Nucleolin as a c-myc G-quadruplex-binding Protein

González¹,

Guo

Hurley³

et al. 2009

Journal of Biological Chemistry

281

329

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“…Recently, we have synthesized a novel carbazole derivative of 3,6-bis[2-(1-methylpyridinium)vinyl]carbazole diiodide (BMVC; Scheme) to stabilize the quadruplex structure of d(T 2 AG 3 ) 4 (Hum) [22] and to illustrate its distinct fluorescence properties [23]. We found that the melting temperature of the quadruplex structure of Hum increases by ca.…”

mentioning

confidence: 99%

A Novel Carbazole Derivative, BMVC: a Potential Antitumor Agent and Fluorescence Marker of Cancer Cells

Chang

Kuo

Lin³

et al. 2004

Chemistry & Biodiversity

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We have investigated a novel compound, 3,6-bis[2-(1-methylpyridinium)vinyl]carbazole diiodide (BMVC), for inhibiting telomerase activity and distinguishing human lung H1299 and oral Ca9-22 cancer cells from lung IMR90 and skin Detroit-551 normal fibroblast cells. The telomeric repeat amplification protocol (TRAP) assay shows that the concentration of BMVC that inhibits 50% of the telomerase activity (IC50) is ca. 0.05 microM. On the other hand, the cell-viability assay indicates that the cytotoxicity was less than 15% to the H1299 and Ca9-22 cancer cells, and almost negligible to the MRC-5 and Detroit-551 normal cells after incubation with 0.5 microM BMVC for 72 h. The low concentration of 0.05 microM of BMVC can inhibit telomerase activity but does not have general toxic effects to normal cells, implying that BMVC is a promising telomerase inhibitor. Moreover, wide-field fluorescence images of 0.1 microM BMVC-treated cells show bright fluorescence spots in the nuclei of the most H1299 and Ca9-22 cancer cells. Interestingly, similar fluorescence spots are hardly observed in the nuclei of the IMR90 and Detroit-551 normal cells, implying that BMVC might be a useful marker to distinguish tumor cells and normal cells.

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“…In comparison, the enhancement of BMVC fluorescence is slightly lower upon interaction with HT24 (quadruplex) than that of LD12 (duplex) in our previous work. 22 Fluorescence titration was carried out to measure the binding affinities of o-BMVC to LD12 and HT24. Figure 3 shows the fluorescence spectra of 10 μm of o-BMVC by adding DNA from 0.25 to 8 μm.…”

Section: Confocal Microscopymentioning

confidence: 99%

Fluorescent probe for visualizing guanine-quadruplex DNA by fluorescence lifetime imaging microscopy

et al. 2013

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Abstract. The importance of guanine-quadruplex (G4) is not only in protecting the ends of chromosomes for human telomeres but also in regulating gene expression for several gene promoters. However, the existence of G4 structures in living cells is still in debate. A fluorescent probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), for differentiating G4 structures from duplexes is characterized. o-BMVC has a large contrast in fluorescence decay time, binding affinity, and fluorescent intensity between G4 structures and duplexes, which makes it a good candidate for probing G4 DNA structures. The fluorescence decay time of o-BMVC upon interaction with G4 structures of telomeric G-rich sequences is ∼2.8 ns and that of interaction with the duplex structure of a calf thymus is ∼1.2 ns. By analyzing its fluorescence decay time and histogram, we were able to detect one G4 out of 1000 duplexes in vitro. Furthermore, by using fluorescence lifetime imaging microscopy, we demonstrated an innovative methodology for visualizing the localization of G4 structures as well as mapping the localization of different G4 structures in living cells. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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A Fluorescent Carbazole Derivative: High Sensitivity for Quadruplex DNA

Cited by 130 publications

References 29 publications

Identification and Characterization of Nucleolin as a c-myc G-quadruplex-binding Protein

Identification and Characterization of Nucleolin as a c-myc G-quadruplex-binding Protein

A Novel Carbazole Derivative, BMVC: a Potential Antitumor Agent and Fluorescence Marker of Cancer Cells

Fluorescent probe for visualizing guanine-quadruplex DNA by fluorescence lifetime imaging microscopy

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