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G quadruplex

Yi-Lin Wu, Noah E Horwitz, Kan-Sheng Chen, Diego A Gomez-Gualdron, Norman S Luu, Lin Ma, Timothy C Wang, Mark C Hersam, Joseph T Hupp, Omar K Farha, Randall Q Snurr, Michael R Wasielewski
Two-dimensional covalent organic frameworks often π stack into crystalline solids that allow precise spatial positioning of molecular building blocks. Inspired by the hydrogen-bonded G-quadruplexes found frequently in guanine-rich DNA, here we show that this structural motif can be exploited to guide the self-assembly of naphthalene diimide and perylene diimide electron acceptors end-capped with two guanine electron donors into crystalline G-quadruplex-based organic frameworks, wherein the electron donors and acceptors form ordered, segregated π-stacked arrays...
May 2017: Nature Chemistry
Lena Grimmelsmann, Alireza Marefat Khah, Christian Spies, Christof Hättig, Patrick Nuernberger
Many synthetic DNA minor groove binders exhibit a strong increase in fluorescence when bound to DNA. The pharmaceutical-relevant berenil (diminazene aceturate) is an exception with an extremely low fluorescence quantum yield (on the order of 10(-4)). We investigate the ultrafast excited-state dynamics of this triazene by femtosecond time-resolved fluorescence experiments in water, ethylene glycol, and buffer and bound to the enzyme β-trypsin, the minor groove of AT-rich DNA, and G-quadruplex DNA. Ab initio calculations provide additional mechanistic insight...
April 20, 2017: Journal of Physical Chemistry Letters
Mrinal Kanti Si, Anik Sen, Bishwajit Ganguly
G-quadruplexes are formed by the association of four guanine bases through Hoogsteen hydrogen bonding in guanine-rich sequences of DNA and exist in the telomere as well as in promoter regions of certain oncogenes. The sequences of G-quadruplex-DNA are targets for the design of molecules that can bind and can be developed as anti-cancer drugs. The linear and cyclic protonated diamines have been explored to bind to G-quadruplex-DNA through hydrogen bonding interactions. The quadruplex-DNA binders exploit π-stacking and hydrogen bonding interactions with the phosphate backbone of loops and grooves...
April 20, 2017: Physical Chemistry Chemical Physics: PCCP
Wezley C Griffin, Jun Gao, Alicia K Byrd, Shubeena Chib, Kevin D Raney
DNA sequences that are guanine-rich have received considerable attention due to their potential to fold into a secondary, four-stranded DNA structure termed G-quadruplex (G4) which has been implicated in genomic instability and some human diseases. We have previously identified positive coactivator of transcription (PC4), a single-stranded DNA (ssDNA) binding protein, as a novel G4 interactor. Here, to expand on these previous observations, we biochemically and biophysically characterized the interaction between PC4 and G4DNA...
April 17, 2017: Journal of Biological Chemistry
V Venkatesh, Narendra Kumar Mishra, Isolda Romero-Canelón, Robbin R Vernooij, Huayun Shi, James P C Coverdale, Abraha Habtemariam, Sandeep Verma, Peter J Sadler
A photoactivatable dopamine-conjugated platinum(IV) anticancer complex (Pt-DA) has been incorporated into G-quadruplex G4K(+) borate hydrogels by using borate ester linkages (Pt-G4K(+)B hydrogel). These were characterized by (11)B NMR, attenuated total reflection Fourier transform infrared spectroscopy, circular dichroism, scanning electron microscopy and transmission electron microscopy. Microscopy investigations revealed the transformation of an extended fiber assembly into discrete flakes after incorporation of Pt-DA...
April 17, 2017: Journal of the American Chemical Society
Emmanuel O Ariyo, Evan P Booy, Edis Dzananovic, Ewan K McRae, Markus Meier, Kevin McEleney, Jorg Stetefeld, Sean A McKenna
Intramolecular G-quadruplexes (G4s) are G-rich nucleic acid structures that fold back on themselves via interrupting loops to create stacked planar G-tetrads, in which four guanine bases associate via Hoogsteen hydrogen bonding. The G4 structure is further stabilized by monovalent cations centered between the stacked tetrads. The G-tetrad face on the top and bottom planes of G4s are often the site of interaction with proteins and small molecules. To investigate the potential impact of interrupting loops on both G4 structure and interaction with proteins/small molecules, we characterized a specific G4 from the 3'-UTR of PITX1 mRNA that contains loops of 6 nucleotides using biophysical approaches...
April 12, 2017: Biochemical and Biophysical Research Communications
Dora Maria Răsădean, Bin Sheng, Jyotirmaee Dash, G Dan Pantos
We report herein the design and synthesis of water soluble, amino acid functionalised naphthalenediimides (NDIs) as potential ligands of native G quadruplexes. The NDIs have been tested on a panel of oncogene promoters and also on the human telomeric sequence h-telo and double-strand DNA. Out of the ligands tested, NDI 3 (Nε Boc-L lysine protected NDI) exhibited a highly discriminating nature, stabilising only the oncogene promoter c kit2, which is up-regulated up to 80% in ovarian, gastrointestinal and breast malignancies...
April 13, 2017: Chemistry: a European Journal
Qian Li, Shuaihua Li, Xiu Chen, Liujiao Bian
A basket-type G-quadruplex (GQ) fluorescent oligonucleotide (OND) probe is designed to detect iodides dependent on thymine-Hg(II)-thymine (T-Hg(II)-T) base pairs and the intrinsic fluorescence quenching capacity of GQ. In the presence of Hg(II) ions (Hg(2+)), the two hexachloro-fluorescein-labeled ONDs form a hairpin structure and the fluorophores are dragged close to the GQ, leading to fluorescence quenching of the probe due to photoinduced electron transfer. Upon addition of iodide anions, Hg(2+) are extracted from T-Hg(II)-T complexes which attributes to the stronger binding with iodide anions, resulting in the fluorescence recovery...
September 1, 2017: Food Chemistry
Anna Aviñó, Maria Dellafiore, Raimundo Gargallo, Carlos González, Adolfo M Iribarren, Javier Montserrat, Ramon Eritja
G-quadruplex and i-motif are tetraplex structures present in telomeres and promoter regions of oncogenes. The possibility of producing nanodevices with pH-sensitive functions has triggered the interest for modified oligonucleotides with improved structural properties. We synthesized C-rich oligonucleotides carrying conformationally restricted (2'S)-2'-deoxy-2'-C-methyl-cytidine units. The effect of this modified nucleoside on the stability of intramolecular i-motifs related to vertebrate telomere was investigated by means of spectroscopic methods (UV, CD and NMR)...
April 13, 2017: Chembiochem: a European Journal of Chemical Biology
Amanda C Hall, Lauren A Ostrowski, Violena Pietrobon, Karim Mekhail
Cells have evolved intricate mechanisms to maintain genome stability despite allowing mutational changes to drive evolutionary adaptation. Repetitive DNA sequences, which represent the bulk of most genomes, are a major threat to genome stability often driving chromosome rearrangements and disease. The major source of repetitive DNA sequences and thus the most vulnerable constituents of the genome are the rDNA (rDNA) repeats, telomeres, and transposable elements. Maintaining the stability of these loci is critical to overall cellular fitness and lifespan...
March 4, 2017: Nucleus
Joanna Kosman, Jacqueline Jatschka, Andrea Csaki, Wolfgang Fritzsche, Bernard Juskowiak, Ondrej Stranik
Peroxidase-mimicking DNAzyme was applied as a catalyst of silver deposition on gold nanoparticles. This DNAzyme is formed when hemin binds to the G-quadruplex-forming DNA sequence. Such a system is able to catalyze a redox reaction with a one- or two-electron transfer. The process of silver deposition was monitored via a localized surface plasmon resonance technique (LSPR), which allows one to record scattering spectrum of a single nanoparticle. Our study showed that DNAzyme is able to catalyze silver deposition...
April 13, 2017: Sensors
Juan A Aguilar, Raquel Belda, Enrique García-España, Gareth A Morris, Jonathan W Steed
The self-assembling tendencies of guanosine-5'-monophosphate (GMP) can be drastically increased using polyamines, with potential applications in the production of biocompatible smart materials, as well as for the design of anti-tumoral drugs based on G-quadruplex stabilization. Results from scanning electron microscopy (SEM), wide angle X-ray scattering (WAXS), rheology and nuclear magnetic resonance (NMR) z-spectroscopy studies are presented.
April 12, 2017: Chemistry: a European Journal
Xiaolu Hu, Chao Li, Chang Feng, Xiaoxia Mao, Yang Xiang, Genxi Li
A simple colorimetric assay is developed for the sensitive and selective detection of an antibody, which combines a protein binding-induced signaling approach with a novel DNAzyme-based conformational switching strategy.
April 12, 2017: Chemical Communications: Chem Comm
Andong Zhao, Suzanne E Howson, Chuanqi Zhao, Jinsong Ren, Peter Scott, Chunyu Wang, Xiaogang Qu
The design and synthesis of metal complexes that can specifically target DNA secondary structure has attracted considerable attention. Chiral metallosupramolecular complexes (e.g. helicates) in particular display unique DNA-binding behavior, however until recently few examples which are both water-compatible and enantiomerically pure have been reported. Herein we report that one metallohelix enantiomer , available from a diastereoselective synthesis with no need for resolution, can enantioselectively stabilize human telomeric hybrid G-quadruplex and strongly inhibit telomerase activity with IC 50 of 600 nM...
April 8, 2017: Nucleic Acids Research
Shuzhen Yue, Tingting Zhao, Hongjie Qi, Yongcun Yan, Sai Bi
A toehold-mediated strand displacement (TMSD)-based cross-catalytic hairpin assembly (C-CHA) is demonstrated in this study, achieving exponential amplification of nucleic acids. Functionally, this system consists of four hairpins (H1, H2, H3 and H4) and one single-stranded initiator (I). Upon the introduction of I, the first CHA reaction (CHA1) is triggered, leading to the self-assembly of hybrid H1·H2 that then initiates the second CHA reaction (CHA2) to obtain the hybrid H3·H4. Since the single-stranded region in H3·H4 is identical to I, a new CHA1 is initiated, which thus achieves cross operation of CHA1 and CHA2 and exponential growth kinetics...
April 4, 2017: Biosensors & Bioelectronics
Dorota Piekna-Przybylska, Gaurav Sharma, Sanjay B Maggirwar, Robert A Bambara
Viruses can interact with host cell molecules responsible for the recognition and repair of DNA lesions, resulting in dysfunctional DNA damage response (DDR). Cells with inefficient DDR are more vulnerable to therapeutic approaches that target DDR, thereby raising DNA damage to a threshold that triggers apoptosis. Here, we demonstrate that 2 Jurkat-derived cell lines with incorporated silent HIV-1 provirus show increases in DDR signaling that responds to formation of double strand DNA breaks (DSBs). We found that phosphorylation of histone H2AX on Ser139 (gamma-H2AX), a biomarker of DSBs, and phosphorylation of ATM at Ser1981, Chk2 at Thr68, and p53 at Ser15, part of signaling pathways associated with DSBs, are elevated in these cells...
April 7, 2017: Cell Cycle
Mahdi Zeraati, Aaron L Moye, Jason W H Wong, Dilmi Perera, Mark J Cowley, Daniel U Christ, Tracy M Bryan, Marcel E Dinger
Cancer is a multifactorial disease driven by a combination of genetic and environmental factors. Many cancer driver mutations have been characterised in protein-coding regions of the genome. However, mutations in noncoding regions associated with cancer have been less investigated. G-quadruplex (G4) nucleic acids are four-stranded secondary structures formed in guanine-rich sequences and prevalent in the regulatory regions. In this study, we used published whole cancer genome sequence data to find mutations in cancer patients that overlap potential RNA G4-forming sequences in 5' UTRs...
April 6, 2017: Scientific Reports
Sébastien Lyonnais, Aleix Tarrés-Solé, Anna Rubio-Cosials, Anna Cuppari, Reicy Brito, Joaquim Jaumot, Raimundo Gargallo, Marta Vilaseca, Cristina Silva, Anton Granzhan, Marie-Paule Teulade-Fichou, Ramon Eritja, Maria Solà
No abstract text is available yet for this article.
April 6, 2017: Scientific Reports
Samuel Rouleau, Rachel Jodoin, Jean-Michel Garant, Jean-Pierre Perreault
G-Quadruplexes are non-canonical secondary structures that can be adopted under physiological conditions by guanine-rich DNA and RNA molecules. They have been reported to occur, and to perform multiple biological functions, in the genomes and transcriptomes of many species, including humans. This chapter focuses specifically on RNA G-quadruplexes and reviews the most recent discoveries in the field, as well as addresses the upcoming challenges researchers studying these structures face.
April 6, 2017: Advances in Biochemical Engineering/biotechnology
Jiachun Liu, Mei Chen, Yanli Wang, Xiaoyin Zhao, Sijia Wang, Yanling Wu, Wen Zhang
A novel series of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines were designed, synthesized and evaluated for their antitumor activity against lung adenocarcinoma by CCK-8 assay, electrophoretic mobility shift assay (EMSA), UV-melting study, wound healing assay and docking study. These compounds showed good inhibitory activities against lung adenocarcinoma. Especially compound 12c exhibited potential antiproliferative activity against A549 cell line with the half maximal inhibitory concentration (IC50) value of 1...
March 18, 2017: European Journal of Medicinal Chemistry
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