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G quadruplex

Guangwen Li, Zhijun Li, Xiuhua You, Jinghua Chen, Shurong Tang
A novel label-free electrochemical biosensor for the detection of Hg(2+) based on ligase mediated creation of G-quadruplex-hemin DNAzyme has been developed. Firstly, Cp probe was immobilized on the gold electrode surface through Au-SH bond. In the presence of Hg(2+), Cp and Ap probes were partly hybridized with the LJ probe respectively through the specific T-Hg(2+)-T interaction. Then, the adjacent 3'-OH terminal of Cp will link with the 5'-PO4 terminal of Ap to form a G-rich DNA at the function of T4-ligase...
December 1, 2016: Talanta
Hong-Xin Jiang, Zhen-Zhen Liang, Yan-Hong Ma, De-Ming Kong, Zhang-Yong Hong
Real-time PCR has revolutionized PCR from qualitative to quantitative. As an isothermal DNA amplification technique, rolling circular amplification (RCA) has been demonstrated to be a versatile tool in many fields. Development of a simple, highly sensitive, and specific strategy for real-time monitoring of RCA will increase its usefulness in many fields. The strategy reported here utilized the specific fluorescence response of thioflavin T (ThT) to G-quadruplexes formed by RCA products. Such a real-time monitoring strategy works well in both traditional RCA with linear amplification efficiency and modified RCA proceeded in an exponential manner, and can be readily performed in commercially available real-time PCR instruments, thereby achieving high-throughput detection and making the proposed technique more suitable for biosensing applications...
November 2, 2016: Analytica Chimica Acta
Petr Stadlbauer, Liuba Mazzanti, Tristan Cragnolini, David J Wales, Philippe Derreumaux, Samuela Pasquali, Jiri Sponer
G-quadruplexes are the most important non-canonical DNA architectures. Many quadruplex-forming sequences, including the human telomeric sequence d(GGGTTA)n, have been investigated due to their implications in cancer and other diseases, and because of their potential in DNA-based nanotechnology. Despite availability of atomistic structural studies of folded G-quadruplexes, their folding pathways remain mysterious, and mutually contradicting models of folding coexist in the literature. Recent experiments convincingly demonstrated that G-quadruplex folding often takes days to reach the thermodynamics equilibrium...
October 21, 2016: Journal of Chemical Theory and Computation
Sagar Satpathi, Mandar Kulkarni, Arnab Mukherjee, Partha Hazra
Among different polymorphs of DNA, G-quadruplex (GQ) formation in guanine rich sequences has received special attention due to its direct relevance to cellular aging and abnormal cell growths. To date, smaller ions like Na(+), K(+), Li(+), and NH4(+) are the best possible selective GQ stabilizing materials. Herein, we report that an ionic liquid (IL), i.e. guanidinium tris(pentafluoroethyl)trifluorophosphate, can not only instigate the GQ formation in the absence of conventional GQ forming ions (like Na(+), K(+), NH4(+), etc...
October 21, 2016: Physical Chemistry Chemical Physics: PCCP
Maria Prokofjeva, Vladimir Tsvetkov, Dmitry Basmanov, Anna Varizhuk, Maria Lagarkova, Igor Smirnov, Kirill Prusakov, Dmitry Klinov, Vladimir Prassolov, Galina Pozmogova, Sergey N Mikhailov
New natural and chemically modified DNA aptamers that inhibit HIV-1 activity at submicromolar concentrations (presumably via preventing viral entry into target cells) are reported. The new DNA aptamers were developed based on known intramolecular G-quadruplexes (G4s) that were functionally unrelated to HIV inhibition [the thrombin-binding aptamer and the fragment of the human oncogene promoter (Bcl2)]. The majority of previously described DNA inhibitors of HIV infection adopt intermolecular structures, and thus their folding variability represents an obvious disadvantage...
October 20, 2016: Nucleic Acid Therapeutics
Maryam Ghahremani Nasab, Leila Hassani, Sara Mohammadi Nejad, Davood Norouzi
A DNA enzyme with peroxidase activity is a G-quadruplex-based DNAzyme formed by hemin and G-quadruplex DNA. Activity of peroxide DNAzymes can be influenced by the structure of quadruplex DNA. In this investigation, the interaction of hemin with T30695 G-quadruplex DNA is evaluated. Molecular dynamic simulation indicates that the binding mode of hemin to G-quadruplex DNA is end-stacking, which is consistent with absorption spectroscopy. Based on fluorescence spectroscopy, hemin ejects thiazole orange from bases of four-strand DNA...
October 17, 2016: Journal of Biological Physics
Aaron M Fleming, Yun Ding, Anton Alenko, Cynthia J Burrows
Zika virus has emerged as a global concern because neither a vaccine nor antiviral compounds targeting it exist. A structure for the positive-sense RNA genome has not been established, leading us to look for potential G-quadruplex sequences (PQS) in the genome. The analysis identified >60 PQSs in the Zika genome. To minimize the PQS population, conserved sequences in the Flaviviridae family were found by sequence alignment, identifying seven PQSs in the prM, E, NS1, NS3, and NS5 genes. Next, alignment of 78 Zika strain genomes identified a unique PQS near the end of the 3'-UTR...
October 14, 2016: ACS Infectious Diseases
Sang C Lee, Jack Zhang, Josh Strom, Danzhou Yang, Thai Nho Dinh, Kyle Kappeler, Qin M Chen
Inhibition of protein synthesis serves as a general measure of cellular consequence to chemical stress. A few proteins are translated selectively and influence cell fate. How these proteins can bypass the general control of translation remains unknown. We found that low to mild doses of oxidants induce de novo translation of NRF2 protein. Here we demonstrate the presence of a G-quadruplex structure in 5' Untranslated Region (5' UTR) of NRF2 mRNA, as measured by Circular Dichroism, Nuclear Magnetic Resonance, and Dimethylsulfate Footprinting...
October 10, 2016: Molecular and Cellular Biology
Michael A Terzidis, Andreea Prisecaru, Zara Molphy, Niall Barron, Antonio Randazzo, Elise Dumont, Marios G Krokidis, Andrew Kellett, Chryssostomos Chatgilialoglu
Herein we report the quantification of purine lesions arising from gamma-radiation sourced hydroxyl radicals (HO(•)) on tertiary dsDNA helical forms of supercoiled (SC), open circular (OC) and linear (L) conformation, along with single-stranded folded and non-folded sequences of guanine rich DNA in selected G-quadruplex structures. We identify that DNA helical topology and folding plays major, and unexpected, roles in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA), along with tandem-type purine lesions 5',8-cyclo-2'-deoxyguanosine (5',8-cdG) and 5',8-cyclo-2'-deoxyadenosine (5',8-cdA)...
October 13, 2016: Free Radical Research
Rong-Peng Peng, Ling-Bao Xing, Xiao-Jun Wang, Cheng-Juan Wu, Bin Chen, Hai-Feng Ji, Li-Zhu Wu, Chen-Ho Tung
We developed a novel Pb(2+)-sensor based on a microcantilever that was modified with a specific Pb(2+)-dependent DNAzyme molecule. This microcantilever sensor could detect Pb(2+) sensitively and selectively in an aqueous solution. Upon complexation with Pb(2+), the DNAzyme duplex unwinded and formed a G-quadruplex conformation, which led to an increase of repulsion between the DNAzyme molecules and a subsequent bending of the microcantilever. This microcantilever sensor could be regenerated, flowing through a strong Pb(2+) chelator, 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid...
2016: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
Ling Zhang, Jens Ulstrup, Jingdong Zhang
DNA quadruplexes (qs) are a class of "non-canonical" oligonucleotides (OGNs) composed of stacked guanine (G) quartets stabilized by specific cations. Metal porphyrins selectively bind to G-qs complexes to form what is known as DNAzyme, which can exhibit peroxidase and other catalytic activity similar to heme group metalloenzymes. In the present study we investigate the electrochemical properties and the structure of DNAzyme monolayers on single-crystal Au(111)-electrode surfaces using cyclic voltammetry and scanning tunnelling microscopy under electrochemical potential control (in situ STM)...
September 20, 2016: Faraday Discussions
Yoojin Park, Ki Tae Kim, Byeang Hyean Kim
We have developed a simple and sensitive system for detecting AGG trinucleotide repeats through the formation of intermolecular G-quadruplexes using a fluorescent oligonucleotide. The fluorescence signal increased rapidly and dramatically by 44.7-fold with respect to the low background signal in the presence of RNA agg repeats and by 35.0-fold in the presence of DNA AGG repeats.
October 20, 2016: Chemical Communications: Chem Comm
Beata Klejevskaja, Alice L B Pyne, Matthew Reynolds, Arun Shivalingam, Richard Thorogate, Bart W Hoogenboom, Liming Ying, Ramon Vilar
We have developed self-assembled DNA mini-circles that contain a G-quadruplex-forming sequence from the c-Myc oncogene promoter and demonstrate by FRET that the G-quadruplex unfolding kinetics are 10-fold slower than for the simpler 24-mer G-quadruplex that is commonly used for FRET experiments.
October 13, 2016: Chemical Communications: Chem Comm
Kumar Padmapriya, Ritu Barthwal
Binding of coralyne to tetra-molecular parallel G-quadruplex DNA [d(TTGGGGT)]4 was evaluated for the first time using biophysical techniques. Absorbance titrations show hypo/hyper-chromism accompanied by 12nm red shift with binding constant Kb=0.2-4.0×10(6)M(-1). Binding induces a negative circular dichroism band of coralyne at 315nm. Quenching of fluorescence (~64%) along with 10nm blue shift in emission maxima indicates proximity of coralyne to guanine bases. Job plot indicates existence of multiple complexes...
October 1, 2016: Biophysical Chemistry
Jen-Yu Liao, Irina Anosova, Saikat Bala, Wade D Van Horn, John C Chaput
G-rich sequences can adopt four-stranded helical structures, called G-quadruplexes, that self-assemble around monovalent cations like sodium (Na(+) ) and potassium (K(+) ). Whether similar structures can be formed from xeno-nucleic acid (XNA) polymers with a shorter backbone repeat unit is an unanswered question with significant implications on the fold space of functional XNA polymers. Here, we examine the potential for TNA (α-L-threofuranosyl nucleic acid) to adopt a four-stranded helical structure based on a planar G-quartet motif...
October 7, 2016: Biopolymers
Xin-Min Li, Ke-Wei Zheng, Yu-Hua Hao, Zheng Tan
A guanine-vacancy-bearing G-quadruplex (GVBQ) interacts with guanine and derivatives by a structural complementation to form a more stable and intact G-quadruplex. Sensors using GVBQs are devised to detect guanine and other nucleobases, and their derivatives derived from structurally similar compounds. A strict requirement of Hoogsteen hydrogen bonds between the GVBQ and analyte in the structural complementation confers exceptional selectivity on the analyte. As such, subtle modifications on analytes affecting even a single hydrogen bond can preclude the recognition...
October 24, 2016: Angewandte Chemie
Kaori Tsukakoshi, Yuri Ikuta, Koichi Abe, Wataru Yoshida, Keisuke Iida, Yue Ma, Kazuo Nagasawa, Koji Sode, Kazunori Ikebukuro
We report that a G-quadruplex-specific compound induced structural changes in G-quadruplex-forming DNA aptamers and stabilized the folded structures, making them suitable for targeted proteins and enhancing their binding properties.
October 18, 2016: Chemical Communications: Chem Comm
Jian Li, Jingjin Zhao, Shuting Li, Liangliang Zhang, Yong Huang, Shulin Zhao, Yi-Ming Liu
We have developed an electrophoresis separation assisted G-quadruplex DNAzyme-based chemiluminescence (CL) signal amplification strategy on a microchip platform for the detection of trace microRNA. This strategy exhibits high sensitivity and specificity for detection of target molecules.
September 12, 2016: Chemical Communications: Chem Comm
Yanjing Yang, Jin Huang, Xiaohai Yang, Ke Quan, Nuli Xie, Min Ou, Jinlu Tang, Kemin Wang
Due to the effective properties of the FRET signal and K(+)-sensitive recognition of G-quadruplex, aptamer-based FRET nanoflares were developed to sense intracellular potassium ions.
September 15, 2016: Chemical Communications: Chem Comm
Junjie U Guo, David P Bartel
In vitro, some RNAs can form stable four-stranded structures known as G-quadruplexes. Although RNA G-quadruplexes have been implicated in posttranscriptional gene regulation and diseases, direct evidence for their formation in cells has been lacking. Here, we identified thousands of mammalian RNA regions that can fold into G-quadruplexes in vitro, but in contrast to previous assumptions, these regions were overwhelmingly unfolded in cells. Model RNA G-quadruplexes that were unfolded in eukaryotic cells were folded when ectopically expressed in Escherichia coli; however, they impaired translation and growth, which helps explain why we detected few G-quadruplex-forming regions in bacterial transcriptomes...
September 23, 2016: Science
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