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G quadruplex

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https://www.readbyqxmd.com/read/28342691/indenocinnoline-derivatives-as-g-quadruplex-binders-topoisomerase-ii%C3%AE-inhibitors-and-antiproliferative-agents
#1
Grigoris Zoidis, Alice Sosic, Silvia Da Ros, Barbara Gatto, Claudia Sissi, Fausta Palluotto, Angelo Carotti, Marco Catto
DNA intercalating agents are a consolidated therapeutic option in the treatment of tumor diseases. Starting from previous findings in the antiproliferative efficacy of a series of indeno[1,2-c]cinnoline-11-one derivatives, we performed a suitable decoration of this scaffold by means of a simple and straightforward chemistry, aiming to a) enlarge the planar core to a pentacyclic benzo[h]indeno[1,2-c]cinnoline-13-one and b) introduce a basic head tethered through a simple polymethylene chain. In fluorescence melting and fluorescence intercalator displacement assays, these new compounds displayed fair to very good intercalating properties on different nucleic acid strands, with preference for G-quadruplex sequences...
March 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28338097/the-cellular-protein-hnrnp-a2-b1-enhances-hiv-1-transcription-by-unfolding-ltr-promoter-g-quadruplexes
#2
Matteo Scalabrin, Ilaria Frasson, Emanuela Ruggiero, Rosalba Perrone, Elena Tosoni, Sara Lago, Martina Tassinari, Giorgio Palù, Sara N Richter
G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335318/a-label-free-and-sensitive-fluorescent-qualitative-assay-for-bisphenol-a-based-on-rolling-circle-amplification-exonuclease-iii-combined-cascade-amplification
#3
Xia Li, Juan Song, Qing-Wang Xue, Fu-Heng You, Xia Lu, Yan-Cong Kong, Shu-Yi Ma, Wei Jiang, Chen-Zhong Li
Bisphenol A (BPA) detection in drinking water and food packaging materials has attracted much attention since the discovery that BPA can interfere with normal physiological processes and cause adverse health effects. Here, we constructed a label-free aptamer fluorescent assay for selective and sensitive detection of BPA based on the rolling circle amplification (RCA)/Exonuclease III (Exo III)-combined cascade amplification strategy. First, the duplex DNA probe (RP) with anti-BPA aptamer and trigger sequence was designed for BPA recognition and signal amplification...
October 21, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335314/effects-of-g-quadruplex-topology-on-electronic-transfer-integrals
#4
Wenming Sun, Daniele Varsano, Rosa Di Felice
G-quadruplex is a quadruple helical form of nucleic acids that can appear in guanine-rich parts of the genome. The basic unit is the G-tetrad, a planar assembly of four guanines connected by eight hydrogen bonds. Its rich topology and its possible relevance as a drug target for a number of diseases have stimulated several structural studies. The superior stiffness and electronic π-π overlap between consecutive G-tetrads suggest exploitation for nanotechnologies. Here we inspect the intimate link between the structure and the electronic properties, with focus on charge transfer parameters...
October 15, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28330874/high-resolution-3d-nmr-structure-of-the-kras-proto-oncogene-promoter-reveals-key-features-of-a-g-quadruplex-involved-in-transcriptional-regulation
#5
Abdelaziz Kerkour, Julien Marquevielle, Stefaniia Ivashchenko, Liliya A Yatsunyk, Jean-Louis Mergny, Gilmar F Salgado
Non-canonical base pairing within guanine-rich DNA and RNA sequences can produce G-quartets, whose stacking leads to the formation of a G-quadruplex (G4). G4s can coexist with canonical duplex DNA in the human genome and have been suggested to suppress gene transcription, and much attention has therefore focused on studying G4s in promotor regions of disease-related genes. For example, the human KRAS proto-oncogene contains a nuclease-hypersensitive element (1) located upstream of the major transcription start site...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28329689/the-human-cchc-type-zinc-finger-nucleic-acid-binding-protein-binds-g-rich-elements-in-target-mrna-coding-sequences-and-promotes-translation
#6
Daniel Benhalevy, Sanjay K Gupta, Charles H Danan, Suman Ghosal, Hong-Wei Sun, Hinke G Kazemier, Katrin Paeschke, Markus Hafner, Stefan A Juranek
The CCHC-type zinc finger nucleic acid-binding protein (CNBP/ZNF9) is conserved in eukaryotes and is essential for embryonic development in mammals. It has been implicated in transcriptional, as well as post-transcriptional, gene regulation; however, its nucleic acid ligands and molecular function remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and function. We used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327752/umbrella-sampling-molecular-dynamics-simulations-reveal-concerted-ion-movement-through-g-quadruplex-dna-channels
#7
Parisa Akhshi, Gang Wu
We have applied the umbrella sampling (US) method in all-atom molecular dynamics (MD) simulations to obtain potential of mean force (PMF) profiles for ion transport through three representative G-quadruplex DNA channels: [d(TG4T)]4, [d(G3T4G4)]2, and d[G4(T4G4)3]. The US MD results are in excellent agreement with those obtained previously with the adaptive biasing force (ABF) method. We then utilized the unique features in the US MD method to investigate multi-ion effects in [d(G3T4G4)]2 and discovered that the concerted ion movement is crucial for fully explaining the unusual experimental results on ion movement in this particular G-quadruplex system...
March 22, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28324509/human-telomeric-g-quadruplex-structures-and-g-quadruplex-interactive-compounds
#8
Clement Lin, Danzhou Yang
G-quadruplexes are noncanonical secondary structures formed in DNA sequences containing consecutive runs of guanines. It has been shown that the 3' G-rich single-stranded overhangs of human telomeres can form G-quadruplex structures, and the human telomeric DNA G-quadruplexes are considered attractive targets for anticancer drugs. G-quadruplex-interactive compounds have been shown to inhibit telomerase access as well as telomere capping. Nuclear magnetic resonance (NMR) spectroscopy is a powerful method in determining the G-quadruplex structures under physiologically relevant conditions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28322930/engineered-domain-swapping-indicates-context-dependent-functional-role-of-rna-g-quadruplexes
#9
Debmalya Bhattacharyya, Mark J Morris, Prakash Kharel, Gayan Mirihana Arachchilage, Katy M Fedeli, Soumitra Basu
RNA domain swapping typically demonstrates conservation of the native function of the domain in a non-native context. In contrast, we employed RNA engineering to demonstrate deviation of G-quadruplex (GQ) function that is contingent upon its context dependent location, which is opposite to their native functional role. Known translation repressing RNA GQs were engineered into human VEGF IRES A replacing the endogenous GQ domain essential for translation. Alternatively, the translation inhibitory GQ motif within the 5'-UTR of MT3-MMP mRNA was replaced with two known GQ motifs that are essential for translation...
March 16, 2017: Biochimie
https://www.readbyqxmd.com/read/28319903/fe-iii-based-metal-organic-framework-derived-core-shell-nanostructure-sensitive-electrochemical-platform-for-high-trace-determination-of-heavy-metal-ions
#10
Zhihong Zhang, Hongfei Ji, Yingpan Song, Shuai Zhang, Minghua Wang, Changchang Jia, Jia-Yue Tian, Linghao He, Xiaojing Zhang, Chun-Sen Liu
A new core-shell nanostructured composite composed of Fe(III)-based metal-organic framework (Fe-MOF) and mesoporous Fe3O4@C nanocapsules (denoted as Fe-MOF@mFe3O4@mC) was synthesized and developed as a platform for determining trace heavy metal ions in aqueous solution. Herein, the mFe3O4@mC nanocapsules were prepared by calcining the hollow Fe3O4@C that was obtained using the SiO2 nanoparticles as the template, followed by composing the Fe-MOF. The Fe-MOF@mFe3O4@mC nanocomposite demonstrated excellent electrochemical activity, water stability and high specific surface area, consequently resulting in the strong biobinding with heavy-metal-ion-targeted aptamer strands...
March 7, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28318229/tracing-effects-of-fluorine-substitutions-on-g-quadruplex-conformational-changes
#11
Jonathan Dickerhoff, Linn Haase, Walter Langel, Klaus Weisz
A human telomere sequence that folds into an intramolecular (3+1)-hybrid G-quadruplex was modified by the incorporation of 2'-fluoro-2'-deoxyriboguanosines ((F)G) into syn positions of its outer tetrad. A circular dichroism and NMR spectral analysis reveals a nearly quantitative switch of the G-tetrad polarity with concerted syn↔anti transitions of all four G residues. These observations follow findings on a (F)G-substituted (3+1)-hybrid quadruplex with a different fold, suggesting a more general propensity of hybrid-type quadruplexes to undergo a tetrad polarity reversal...
March 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28317975/exposing-the-g-quadruplex-to-electric-fields-the-role-played-by-telomeres-in-the-propagation-of-dna-errors
#12
José Pedro Cerón-Carrasco, Denis Jacquemin
To protect their core machinery from the attack of exogenous agents, cells locate DNA in their nucleus. Nevertheless, some reactive chemical species and physical agents might reach DNA and alter its natural double helix structure. For instance, pulsed electric fields can be used to selectively rewrite the stored genetic information. However, for such modification to be effective, one needs, as a prerequisite, that the replication mechanism is not stopped by the field, so that the changes propagate over the following generations...
March 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28317958/the-collective-behavior-of-spring-like-motifs-tethered-to-a-dna-origami-nanostructure
#13
E-C Schöneweiß, B Saccà
Dynamic DNA nanotechnology relies on the integration of small switchable motifs at suitable positions of DNA nanostructures, thus enabling the manipulation of matter with nanometer spatial accuracy in a trigger-dependent fashion. Typical examples of such motifs are hairpins, whose elongation into duplexes can be used to perform long-range, translational movements. In this work, we used temperature-dependent FRET spectroscopy to determine the thermal stabilities of distinct sets of hairpins integrated into the central seam of a DNA origami structure...
March 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28315316/label-free-and-rapid-detection-of-atp-based-on-structure-switching-of-aptamers
#14
Danyang Ji, Hongqi Wang, Jia Ge, Lin Zhang, Jianjun Li, Dongmei Bai, Juan Chen, Zhaohui Li
In this work, an aptamer-based fluorescent strategy for label-free detection of ATP was developed by using Thioflavin T (ThT) as a fluorescence indicator, which can specifically bind with G-quadruplex DNAs to generate enhanced fluorescence intensity. In the absence of ATP, the folded structure of ATP aptamer allows the intercalation of ThT to produce strong fluorescence signal. However, upon ATP binding to the aptamer where ThT intercalated, the conformational change or distortion of the aptamer is large enough to cause much less intercalation of ThT and consequently drastic suppression of the fluorescence intensity...
March 14, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28306504/targeting-of-polycomb-repressive-complex-2-to-rna-by-short-repeats-of-consecutive-guanines
#15
Xueyin Wang, Karen J Goodrich, Anne R Gooding, Haroon Naeem, Stuart Archer, Richard D Paucek, Daniel T Youmans, Thomas R Cech, Chen Davidovich
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28296179/the-5-ag%C3%A2-cc-3-fragment-from-the-human-cpeb3-ribozyme-forms-an-ultrastable-parallel-rna-g-quadruplex
#16
Katharina Kulikov, Senada Nozinovic, Stephanie Kath-Schorr
An unusually thermostable G-quadruplex is formed by a sequence fragment of a naturally occurring ribozyme, the human CPEB3 ribozyme. Strong evidence is provided for the formation of a uniquely stable intermolecular G-quadruplex structure consisting of five tetrad layers using CD-spectroscopy, UV-melting curves, two-dimensional NMR spectroscopy and gel shift analysis. The cationic porphyrin TMPyP4 destabilizes the complex.
March 13, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28294495/ultrathin-covalently-bound-organic-layers-on-mica-formation-of-atomically-flat-biofunctionalizable-surfaces
#17
Rickdeb Sen, Digvijay Gahtory, Rui Rijo Carvalho, Bauke Albada, Floris L van Delft, Han Zuilhof
Mica is the substrate of choice for microscopic visualization of a wide variety of intricate nanostructures. Unfortunately, the lack of a facile strategy for its modification has prevented the on-mica assembly of nanostructures. Herein, we disclose a convenient catechol-based linker that enables various surface-bound metal-free click reactions, and an easy modification of mica with DNA nanostructures and a horseradish peroxidase mimicking hemin/G-quadruplex DNAzyme.
March 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28292558/corrigendum-to%C3%A2-a-split-g-quadruplex-based-dna-nano-tweezers-structure-as-a-signal-transducing-molecule-for-the-homogeneous-detection-of-specific-nucleic-acids-biosens-bioelectron-74-2015-222-226
#18
Keisuke Nakatsuka, Hajime Shigeto, Akio Kuroda, Hisakage Funabashi
No abstract text is available yet for this article.
March 11, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28287135/visual-detection-and-differentiation-of-classic-swine-fever-virus-strains-using-nucleic-acid-sequence-based-amplification-nasba-and-g-quadruplex-dnazyme-assay
#19
Xiaolu Lu, Xueyao Shi, Gege Wu, Tiantian Wu, Rui Qin, Yi Wang
The split G-quadruplex DNAzyme has emerged as a valuable tool for visual DNA detection. Here, we successfully integrated colorimetric split G-quadruplex DNAzyme assay with nucleic acid sequence-based amplification to generate a novel detection approach, allowing visual and rapid detection for the RNA of Shimen and HCLV strains of Classic Swine Fever Virus (CSFV). CSFV is a RNA virus that causes a highly contagious disease in domestic pigs and wild boar. With this method, we were able to detect as little as 10 copies/ml of CSF viral RNA within 3 h in serum samples taken from the field...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286728/dna-structural-features-of-eukaryotic-tata-containing-and-tata-less-promoters
#20
Venkata Rajesh Yella, Manju Bansal
Eukaryotic genes can be broadly classified as TATA-containing and TATA-less based on the presence of TATA box in their promoters. Experiments on both classes of genes have revealed a disparity in the regulation of gene expression and cellular functions between the two classes. In this study, we report characteristic differences in promoter sequences and associated structural properties of the two categories of genes in six different eukaryotes. We have analyzed three structural features, DNA duplex stability, bendability, and curvature along with the distribution of A-tracts, G-quadruplex motifs, and CpG islands...
March 2017: FEBS Open Bio
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