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https://www.readbyqxmd.com/read/28731305/the-role-of-lead-ii-in-nucleic-acids
#1
Joana Palou-Mir, Miquel Barceló-Oliver, Roland K O Sigel
Although lead(II) is naturally not associated with nucleic acids, this metal ions has been applied with DNA and RNA in various contexts. Pb2+ is an excellent hydrolytic metal ion for nucleic acids, which is why it is mainly used as probing agent for secondary structure and to determine metal ion binding sites both in vitro and in vivo. A further application of lead(II) is in structural studies, i.e., NMR, but also in X-ray crystallography, mostly using this heavy metal to solve the phase problem in the latter method...
April 10, 2017: Metal Ions in Life Sciences
https://www.readbyqxmd.com/read/28729218/spectroscopic-study-of-fluorescent-probes-based-on-g-quadruplex-oligonucleotides-labeled-with-ethynylpyrenyldeoxyuridine
#2
Angelika Switalska, Ryszard Kierzek, Anna Dembska, Bernard Juskowiak
The design, synthesis, and spectral properties of four pyrene labeled oligonucleotide probes with G-quadruplex structure (Tel22-Tpy, Tel22-Upy, Tel22-6Upy, Tel22-18Upy) based on the 22-mer human telomeric sequence (Tel22) have been reported. Pyrene labels in the form of ethynylpyrenyldeoxyuridine have been inserted efficiently into oligodeoxynucleotides probes using phosphoramidite chemistry. The probes exhibited abilities to fold into G-quadruplex structures and to bind metal cations (Na(+) and K(+)). Folding properties of probes and their spectral behavior were examined by recording the UV-Vis, fluorescence, and CD spectra as well as by analyzing melting profiles...
July 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28728523/structural-insights-into-the-binding-of-small-ligand-molecules-to-a-g-quadruplex-dna-located-in-the-hiv-1-promoter
#3
Petar M Mitrasinovic
Targeting guanine (G)-rich DNA sequences, folded into non-canonical G-quadruplex (G4) structures, by small ligand molecules is a promising strategy for gene therapy of various diseases. There is experimental proposal that, among eight studied ligands, nitidine chloride - NC and a benzo phenanthridine derivative - BPD have the highest binding affinities for such a sequence (5'-T(1)G(2)G(3)C(4)C(5)T(6)G(7)G(8)G(9)C(10)G(11)G(12)G(13)A(14)C(15)T(16)G(17)G(18)G(19)-3') in the HIV-1 promoter, indicating that an anti-HIV-1 prodrug may regulate the expression of the promoter...
July 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28726857/instrument-free-visual-detection-of-tetracycline-on-an-autocatalytic-dna-machine-using-a-caged-g-quadruplex-as-the-signal-reporter
#4
Junhua Chen, Shu Chen, Fengling Li
An instrument-free visual biosensor for the amplified detection of tetracycline has been successfully constructed using an autocatalytic DNA machine as the signal amplifier and a caged G-quadruplex as the signal reporter. The assay is ultrasensitive, enabling the visual detection of trace levels of tetracycline as low as 1 pM without instrumentation.
July 20, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28726387/aryl-substituted-ruthenium-ii-complexes-a-strategy-for-enhanced-photocleavage-and-efficient-dna-binding
#5
Felipe Diógenes Abreu, Tercio de F Paulo, Marcelo H Gehlen, Rômulo A Ando, Luiz G F Lopes, Ana Cláudia S Gondim, Mayron A Vasconcelos, Edson H Teixeira, Eduardo Henrique Silva Sousa, Idalina Maria Moreira de Carvalho
Ruthenium polypyridine complexes have shown promise as agents for photodynamic therapy (PDT) and tools for molecular biology (chromophore-assisted light inactivation). To accomplish these tasks, it is important to have at least target selectivity and great reactive oxygen species (ROS) photogeneration: two properties that are not easily found in the same molecule. To prepare such new agents, we synthesized two new ruthenium complexes that combine an efficient DNA binding moiety (dppz ligand) together with naphthyl-modified (1) and anthracenyl-modified (2) bipyridine as a strong ROS generator bound to a ruthenium complex...
July 20, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28725233/g-quadruplex-in-plants-a-ubiquitous-regulatory-element-and-its-biological-relevance
#6
REVIEW
Vikas Yadav, Hemansi, Nayun Kim, Narendra Tuteja, Puja Yadav
G quadruplexes (G4) are higher-order DNA and RNA secondary structures formed by G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential G4 quadruplex sequences have been identified in G-rich eukaryotic non-telomeric and telomeric genomic regions. Upon function, G4 formation is known to involve in chromatin remodeling, gene regulation and has been associated with genomic instability, genetic diseases and cancer progression. The natural role and biological validation of G4 structures is starting to be explored, and is of particular interest for the therapeutic interventions for human diseases...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28723123/a-both-end-blocked-peroxidase-mimicking-dnazyme-for-low-background-chemiluminescent-sensing-of-mirna
#7
Xianming Li, Houchun Zhang, Yurong Tang, Peng Wu, Shuxia Xu, Xinfeng Zhang
G-quadruplex DNAzymes that exhibited peroxidase-like activity have been shown to be appealing reporters for amplified readout of biosensing events simply by their formation or dissociation in the presence of analytes. For low background signaling, the efficient preblock of DNAzymes is critically important. Herein, we report a both-end blocked DNAzyme beacon strategy for chemiluminescent biosensing. The catalytic activity of peroxidase-mimicking DNAzyme can be inactivated fully by fixing both ends of the DNAzyme sequence, and easily recovered via a strand displace reaction between the miRNA and the block DNA...
June 23, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28720801/mapping-and-characterization-of-g-quadruplexes-in-mycobacterium-tuberculosis-gene-promoter-regions
#8
Rosalba Perrone, Enrico Lavezzo, Erika Riello, Riccardo Manganelli, Giorgio Palù, Stefano Toppo, Roberta Provvedi, Sara N Richter
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome of Mycobacterium tuberculosis and analyse their association to transcription start sites...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717007/epigenetic-suppression-of-human-telomerase-htert-is-mediated-by-the-metastasis-suppressor-nme2-in-a-g-quadruplex-dependent-fashion
#9
Dhurjhoti Saha, Ankita Singh, Tabish Hussain, Vivek Srivastava, Suman Sengupta, Anirban Kar, Parashar Dhapola, Vishnu Dhople, Ramesh Ummani, Shantanu Chowdhury
Transcriptional activation of the human telomerase reverse transcriptase (hTERT) gene, which remains repressed in adult somatic cells, is critical during tumorigenesis. Several transcription factors and the epigenetic state of the hTERT promoter are known to be important for tight control of hTERT in normal tissues, but the molecular mechanisms leading to hTERT reactivation in cancer are not well understood. Surprisingly, here we found occupancy of the metastasis suppressor nonmetastatic 2 (NME2) within hTERT core promoter in HT1080 fibrosarcoma cells and HCT116 colon cancer cells, and NME2 mediated transcriptional repression of hTERT in these cells...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28714689/design-synthesis-and-evaluation-of-new-selective-nm23-h2-binders-as-c-myc-transcription-inhibitors-via-disruption-of-the-nm23-h2-g-quadruplex-interaction
#10
Yu-Qing Wang, Zhou-Li Huang, Shuo-Bin Chen, Chen-Xi Wang, Chan Shan, Qi-Kun Yin, Tian-Miao Ou, Ding Li, Lian-Quan Gu, Jia-Heng Tan, Zhi-Shu Huang
c-MYC is one of the important human proto-oncogenes, and transcriptional factor NM23-H2 can activate c-MYC transcription by recognizing the G-quadruplex in the promoter of the gene. Small molecules that inhibit c-MYC transcription by disrupting the NM23-H2/G-quadruplex interaction might be a promising strategy for developing selective anticancer agents. In recent studies, we developed a series of isaindigotone derivatives, which can bind to G-quadruplex and NM23-H2, thus down-regulating c-MYC (J. Med. Chem...
July 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28707876/fluorescence-light-up-biosensor-for-microrna-based-on-the-distance-dependent-photoinduced-electron-transfer
#11
Shasha Lu, Shuang Wang, Jiahui Zhao, Jian Sun, Xiurong Yang
It is demonstrated that miRNAs exhibit significant regulatory roles in a series of biological processes and associated with diverse human diseases. Herein, we report a convenient fluorescent biosensor for the quantitative determination of miR-21, a key miRNA related to the cardio-cerebrovascular diseases. Our proposal involves not only the rational design of single stranded DNA as the probe, successively including a C-rich sequence as the synthetic template of DNA/Ag nanoclusters (DNA/AgNCs), a complementary (Com) sequence to hybridize with the miR-21 and a G-rich sequence to form complex of G-quadruplex/hemin, but also the distance-dependent property of photoinduced electron transfer (PET) between the preformed DNA/AgNCs (electron donor) and G-quadruplex/hemin complex (electron acceptor)...
July 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28706243/target-guided-synthesis-using-dna-nano-templates-for-selectively-assembling-a-g-quadruplex-binding-c-myc-inhibitor
#12
Deepanjan Panda, Puja Saha, Tania Das, Jyotirmayee Dash
The development of small molecules is essential to modulate the cellular functions of biological targets in living system. Target Guided Synthesis (TGS) approaches have been used for the identification of potent small molecules for biological targets. We herein demonstrate an innovative example of TGS using DNA nano-templates that promote Huisgen cycloaddition from an array of azide and alkyne fragments. A G-quadruplex and a control duplex DNA nano-template have been prepared by assembling the DNA structures on gold-coated magnetic nanoparticles...
July 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28704696/the-function-of-dna-binding-protein-nucleophosmin-in-aav-replication
#13
Stifani Satkunanathan, Robin Thorpe, Yuan Zhao
Adeno-associated viruses (AAV) contain minimal viral proteins necessary for their replication. During virus assembly, AAV acquire, inherently and submissively, various cellular proteins. Our previous studies identified the association of AAV vectors with the DNA binding protein nucleophosmin (NPM1). Nucleophosmin has been reported to enhance AAV infection by mobilizing AAV capsids into and out of the nucleolus, indicating the importance of NPM1 in the AAV life cycle; however the role of NPM1 in AAV production remains unknown...
July 10, 2017: Virology
https://www.readbyqxmd.com/read/28702665/structural-switch-from-a-multistranded-g-quadruplex-to-single-strands-as-a-consequence-of-point-mutation-in-the-promoter-of-the-human-grin1-gene
#14
Swati Chaudhary, Mahima Kaushik, Ritushree Kukreti, Shrikant Kukreti
A huge number of G-rich sequences forming quadruplexes are found in the human genome, especially in telomeric regions, UTRs, and the promoter regions of a number of genes. One such gene is GRIN1 encoding the NR1 subunit of the N-methyl-d-aspartate receptor (NMDA). Several lines of reports have implicated that attenuated function of NMDA results in schizophrenia, a genetic disorder characterized by hallucinations, delusions, and psychosis. Involvement of the GRIN1 gene in the pathogenesis of schizophrenia has been extensively analysed...
July 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28700353/chiral-platinum-ii-4-2-3-dihydroxypropyl-formamide-oxo-aporphine-foa-complexes-promote-tumor-cells-apoptosis-by-directly-targeting-g-quadruplex-dna-in-vitro-and-in-vivo
#15
Qi-Pin Qin, Jiao-Lan Qin, Ming Chen, Yu-Lan Li, Ting Meng, Jie Zhou, Hong Liang, Zhen-Feng Chen
Three platinum(II) complexes, 4 (LC-004), 5 (LC-005), and 6 (LC-006), with the chiral FOA ligands R/S-(±)-FOA (1), R-(+)-FOA (2) and S-(-)-FOA (3), respectively, were synthesized and characterized. As potential anti-tumor agents, these complexes show higher cytotoxicity to BEL-7404 cells than the HL-7702 normal cells. They are potential telomerase inhibitors that target c-myc and human telomeric G-quadruplex DNA. Compared to complexes 4 and 5, 6 exhibited higher binding affinities towards telomeric, c-myc G-quadruplex DNA and caspase-3/9, thereby inducing senescence and apoptosis to a greater extent in tumor cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700110/copper-alkyne-complexation-is-responsible-for-the-nucleolar-localisation-of-quadruplex-nucleic-acid-drugs-labelled-by-click-chemistry
#16
Marie-Paule Teulade-Fichou, Joël Lefebvre, Corinne Guetta, Florent Poyer, Florence Mahuteau-Betzer
G-quadruplex(es) (G4) are non-canonical nucleic acid structures found in guanine-rich sequences. They can be targeted with small molecules (G4-ligands) acting as reporters, for tracking both in vitro and in cells. We explored the cellular localisation of PhenDC3, one of the most powerful G4 ligands, by synthesising two clickable azide and alkyne derivatives (PhenDC3-alk, PhenDC3-az) and labelling them in situ with the corresponding Cy5 click partners. A careful comparison of the results obtained for the copper-based CuAAC and copper-free SPAAC methodologies in fixed cells implicated Cu(I) /alkyne intermediates in the non-specific localisation of ligands (and fluorophores) to the nucleoli...
July 12, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28697478/shedding-lights-on-the-flexible-armed-porphyrins-human-telomeric-g4-dna-interaction-and-cell-photocytotoxicity-research
#17
Xiang-Yu Sun, Ping Zhao, Shu-Fang Jin, Min-Chao Liu, Xia-Hong Wang, Yu-Min Huang, Zhen-Feng Cheng, Si-Qi Yan, Yan-Yu Li, Ya-Qing Chen, Yan-Mei Zhong
DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations...
July 4, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28696445/binding-modes-and-pathway-of-rhps4-to-human-telomeric-g-quadruplex-and-duplex-dna-probed-by-all-atom-molecular-dynamics-simulations-with-explicit-solvent
#18
Kelly Mulholland, Farzana Siddiquei, Chun Wu
RHPS4, a potent binder to human telomeric DNA G-quadruplex, shows high efficacy in tumor cell growth inhibition. However, it's preferential binding to DNA G-quadruplex over DNA duplex (about 10 fold) remains to be improved toward its clinical application. A high resolution structure of the single-stranded telomeric DNA G-quadruplexes, or B-DNA duplex, in complex with RHPS4 is not available yet, and the binding nature of this ligand to these DNA forms remains to be elusive. In this study, we carried out 40 μs molecular dynamics binding simulations with a free ligand to decipher the binding pathway of RHPS4 to a DNA duplex and three G-quadruplex folders (parallel, antiparallel and hybrid) of the human telomeric DNA sequence...
July 11, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28692286/methylated-cytosine-maintains-g-quadruplex-structures-during-polymerase-chain-reaction-and-contributes-to-allelic-dropout
#19
Aaron J Stevens, Martin A Kennedy
The promoter of the human imprinted gene MEST is differentially methylated with respect to the parent of origin and contains several non B-DNA motifs that are capable of forming G-quadruplexes. These factors can contribute to a consistent allelic dropout (ADO) of the maternally methylated DNA during polymerase chain reaction (PCR) analysis of such gene regions. Here, we directly investigate the cause of allelic dropout by applying fluorescent techniques to visualize polymerase amplification and arrest during PCR of differentially methylated DNA templates...
July 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/28686018/detection-of-g-quadruplex-structures-formed-by-g-rich-sequences-from-rice-genome-and-transcriptome-using-combined-probes
#20
Tianjun Chang, Weiguo Li, Zhan Ding, Shaofei Cheng, Kun Liang, Xiangjun Liu, Tao Bing, Dihua Shangguan
Putative G-quadruplex (G4) forming sequences (PQS) are highly prevalent in the genome and transcriptome of various organisms, and are considered as potential regulation elements in many biological processes by forming G4 structures. The formation of G4 structures highly depends on the sequences and the environment. In most cases, it is difficult to predict G4 formation by PQS, especially PQS containing G2 tracts. Therefore, the experimental identification of G4 formation is essential in the study of G4-related biological functions...
July 7, 2017: Analytical Chemistry
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