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G quadruplex

Qingwang Xue, Chunxue Liu, Xia Li, Li Dai, Huaisheng Wang
Various fluorescent sensing systems for miRNAs detection have been developed. But they mostly contain enzymatic amplification reactions and label procedures. The strict reaction conditions of tool enzymes and the high cost of labeling limit their potential applications, especially in complex biological matrix. Here we have addressed the difficult problems and report a strategy for label-free fluorescent DNA dendrimers based on enzyme-free nonlinear hybridization chain reaction (HCR)-mediated multiple G-quadruplex for simple, sensitive and selective detection of miRNAs with low-background signal...
March 16, 2018: Bioconjugate Chemistry
F Nici, G Oliviero, A P Falanga, S D'Errico, M Marzano, D Musumeci, D Montesarchio, S Noppen, C Pannecouque, G Piccialli, N Borbone
By combining the ability of short G-rich oligodeoxyribonucleotides (ODNs) containing the sequence 5'CGGA3' to form higher order G-quadruplex (G4) complexes with the tetra-end-linked (TEL) concept to produce aptamers targeting the HIV envelope glycoprotein 120 (gp120), three new TEL-ODNs (1-3) having the sequence 5'CGGAGG3' were synthesized with the aim of studying the effect of G4 dimerization on their anti-HIV activity. Furthermore, in order to investigate the effect of the groups at the 5' position, the 5' ends of 1-3 were left uncapped (1) or capped with either the lipophilic dimethoxytrityl (DMT) (2) or the hydrophilic glucosyl-4-phosphate (3) moieties...
March 15, 2018: Organic & Biomolecular Chemistry
Ergin Yalçın, Halil Duyar, Heiko Ihmels, Zeynel Seferoğlu
An improved microwave-induced synthesis of five ethidium derivatives (Ethidium derivatives, 2a-d) is presented. As the derivatives 2a-d have been proposed previously to be telomerase inhibitors, the binding interactions of these ethidium derivatives with G-quadruplex DNA were evaluated by means of photometric and fluorimetric titration, thermal DNA denaturation, CD and1 H NMR spectroscopy. In particular, the compound bearing 3,8-bis(pyrrolidin-1-yl)propanamido substituent 2a exhibits high selectivity for G-quadruplex DNA relative to duplex DNA...
May 5, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Gayan Mirihana Arachchilage, Prakash Kharel, Joshua Reid, Soumitra Basu
Since the elevated levels of microRNAs (miRNAs) often cause various diseases, selective inhibition of miRNA maturation is an important therapeutic strategy. Commonly used anti-miRNA strategies are limited to targeting of mature miRNAs, as the upstream targeting of miRNA maturation with an oligonucleotide is challenging due to the presence of stable pre-miRNA stem-loop structure. Previously, we reported that about 16% of known human pre-miRNAs have the potential to adopt G-quadruplex (GQ) structures alternative to canonical stem-loops...
March 12, 2018: ACS Chemical Biology
Jeremy E B McCallum, Christopher W Coyle, Ryan R Elson, Blake A Titterington
The development of small molecules to stabilize the G-quadruplex structure has garnered significant attention for anticancer drug discovery. Herein, we report the synthesis of several 4,4'-diaminoazobenzene derivatives containing different substituent groups and their ability to bind and stabilize telomeric G-quadruplex DNA. Circular dichroism (CD) spectroscopy was performed to characterize the quadruplex topologies, measure stabilization effects, and evaluate their capabilities for conformational photoregulation...
March 12, 2018: Nucleosides, Nucleotides & Nucleic Acids
Sara Lago, Matteo Nadai, Monica Rossetto, Sara N Richter
BACKGROUND: G-quadruplexes (G4s) are nucleic acids secondary structures formed in guanine-rich sequences. Anti-G4 antibodies represent a tool for the direct investigation of G4s in cells. Surface Plasmon Resonance (SPR) is a high sensitive technology, suitable for assessing the affinity between biomolecules. We here aimed at improving the orientation of an anti-G4 antibody (1H6) on SPR sensor chip for optimizing the detection of binding antigens. METHODS: SPR was employed for the characterization of 1H6 interaction with G4 and non-G4 oligonucleotides...
March 7, 2018: Biochimica et Biophysica Acta
Hong-Liang Bao, Yan Xu
Growing evidence indicates that RNA G-quadruplexes have important roles in various processes such as transcription, translation, regulation of telomere length, and formation of telomeric heterochromatin. Investigation of RNA G-quadruplex structures associated with biological events is therefore essential to understanding the functions of these RNA molecules. We recently demonstrated that the sensitivity and simplicity of19 F NMR can be used to directly observe higher-order telomeric G-quadruplexes of labeled RNA molecules in vitro and in living cells, as well as their interactions with ligands and proteins...
April 2018: Nature Protocols
Chen Zhou, Haimin Zou, Chengjun Sun, Dongxia Ren, Wei Xiong, Yongxin Li
Based on a novel signal amplification strategy by catalytic hairpin assembly and displacement of G-quadruplex DNA, an enzyme-free, non-label fluorescent aptasensing approach was established for sensitive detection of four tetracycline veterinary drugs in milk. The network consisted of a pair of partially complementary DNA hairpins (HP1 and HP2). The DNA aptamer of four tetracycline veterinary drugs was located at the sticky end of the HP1. The ring region of HP1 rich in G and C could form a stable G-quadruplex structure, which could emit specific fluorescence signal after binding with the fluorescent dye and N-methylmesoporphyrin IX (NMM)...
March 8, 2018: Analytical and Bioanalytical Chemistry
Ana Rita Duarte, Enrico Cadoni, Ana S Ressurreição, Rui Moreira, Alexandra Paulo
Guanine rich nucleic acid sequences able to form four-stranded structures (G-quadruplexes, G4) play key cellular regulatory roles and are considered as promising drug targets for anticancer therapy. Based on the organization of their structural elements, G4 ligands can be divided into three major families: 1) fused hetero-aromatic polycyclic systems; 2) macrocycles and 3) modular aromatic compounds. The design of modular G4 ligands emerged as the answer to achieve not only more drug-like compounds, but also more selective ligands by targeting G4 loops and grooves diversity...
March 7, 2018: ChemMedChem
Ling Zhang, Kasper P Kepp, Jens Ulstrup, Jingdong Zhang
Metalloporphyrins are active sites in metalloproteins and synthetic catalysts. They have also been studied extensively by electrochemistry as well as being prominent targets in electrochemical scanning tunneling microscopy (STM). Previous studies of FePPIX adsorbed on graphite and alkylthiol modified Au electrodes showed a pair of reversible Fe(III/II)PPIX peaks at about -0.41 V (vs. NHE) at high solution pH. We recently used iron protoporphyrin IX (FeP-PIX) as an intercalating probe for long-range electrochemical electron transfer through a G-quadruplex oligonucleo-tide (DNAzyme); this study disclosed two, rather than a single pair of voltammetric peaks with a new and dominating peak, shifted 200 mV positive relative to the  -0...
March 6, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Fadia Ibrahim, Manolis Maragkakis, Panagiotis Alexiou, Zissimos Mourelatos
mRNAs transmit the genetic information that dictates protein production and are a nexus for numerous pathways that regulate gene expression. The prevailing view of canonical mRNA decay is that it is mediated by deadenylation and decapping followed by exonucleolysis from the 3' and 5' ends. By developing Akron-seq, a novel approach that captures the native 3' and 5' ends of capped and polyadenylated RNAs, respectively, we show that canonical human mRNAs are subject to repeated cotranslational and ribosome-phased endonucleolytic cuts at the exit site of the mRNA ribosome channel, in a process that we term ribothrypsis...
March 5, 2018: Nature Structural & Molecular Biology
Sagar Satpathi, Reman K Singh, Arnab Mukherjee, Partha Hazra
Controlling of ligand mediated G-quadruplex DNA (GQ-DNA) formation and stabilization is an important and challenging aspect due to its active involvement in many biologically important processes such as DNA replication, transcription, etc. Here, we have demonstrated that topotecan (TPT), a potential anticancer drug, can instigate the formation and stabilization of GQ-DNA (H24 → GQ-DNA) in the absence of Na+ /K+ ions via circular dichroism, fluorescence, NMR, UV melting and molecular dynamics (MD) simulation studies...
March 5, 2018: Physical Chemistry Chemical Physics: PCCP
Xiaoyu Li, Junjing Li, Caixia Zhu, Xiaohua Zhang, Jinhua Chen
In this work, a new electrochemical immunosensor was developed for prion protein assay based on hybridization chain reaction (HCR) with hemin/G-quadruplex DNAzyme for signal amplification. In this amplification system, the hemin/G-quadruplex DNAzyme simultaneously mimicked the biocatalytic functions for H2 O2 reduction and L-cysteine oxidation. In the presence of L-cysteine, the hemin/G-quadruplex catalyzed the oxidation of L-cysteine to L-cystine. At the same time, H2 O2 was produced under the oxygen condition...
May 15, 2018: Talanta
Kefeng Wu, Changbei Ma, Zhiyi Deng, Ning Fang, Zhenwei Tang, Xingxing Zhu, Kemin Wang
In this paper, we describe a novel, label-free and nicking enzyme-assisted fluorescence signal amplification strategy that demonstrates to be cost efficient, sensitive, and unique for assaying the RNase H activity and inhibition based on G-quadruplex formation using a thioflavin T (ThT) dye. This novel assay method is able to detect RNase H with a detection limit of 0.03 U /mL and further exhibits a good linearity R2 = 0.9923 at a concentration range of 0.03-1 U/mL under optimized conditions. Moreover, the inhibition effect of gentamycin on the RNase H activity is also studied...
May 15, 2018: Talanta
Baozhu Zhang, Chunying Wei
A novel turn-on fluorescent biosensor has been constructed using C-PS2.M-DNA-templated silver nanoclusters (Ag NCs) with an average diameter of about 1 nm. The proposed approach presents a low-toxic, simple, sensitive, and selective detection for Pb2+ . The fluorescence intensity of C-PS2.M-DNA-Ag NCs enhances significantly in the presence of Pb2+ , which is attributed to the special interaction between Pb2+ and its aptamer DNA PS2.M. Pb2+ induces the aptamer to form G-quadruplex and makes two darkish DNA/Ag NCs located at the 3' and 5' terminus close, resulting in the fluorescence light-up...
May 15, 2018: Talanta
Weronika Kotkowiak, Jolanta Lisowiec-Wachnicka, Jakub Grynda, Ryszard Kierzek, Jesper Wengel, Anna Pasternak
Thrombin is a serine protease that plays a crucial role in hemostasis, fibrinolysis, cell proliferation, and migration. Thrombin binding aptamer (TBA) is able to inhibit the activity of thrombin molecule via binding to its exosite I. This 15-nt DNA oligonucleotide forms an intramolecular, antiparallel G-quadruplex structure with a chair-like conformation. In this paper, we report on our investigations on the influence of certain modified nucleotide residues on thermodynamic stability, folding topology, and biological properties of TBA variants...
March 2, 2018: Molecular Therapy. Nucleic Acids
Micol Falabella, Rafael J Fernandez, Brad Johnson, Brett A Kaufman
Some DNA or RNA sequences rich in guanine (G) nucleotides can adopt non-canonical conformations known as G-quadruplexes (G4). In the nuclear genome, G4 motifs have been associated with genome instability and gene expression defects, but they are increasingly recognized to be regulatory structures. Recent studies have revealed that G4 structures can form in the mitochondrial genome (mtDNA) and G4 forming potential sequences are associated with the origin of mtDNA deletions. However, little is known about the regulatory role of G4 structures in mitochondria...
February 28, 2018: Current Medicinal Chemistry
Banhi Biswas, Pooja Kumari, Perumal Vivekanandan
Packaging signals (pac1 and pac2) of human herpesviruses (HHVs) that contain GC-rich elements are essential for cleavage and packaging of the virus. Here, we report the presence of putative G-quadruplex sequences (PQSs) in the packaging signal (pac1) of all HHVs. Importantly, the residues critical for the formation of G-quadruplex structures were highly conserved as compared to those not critical for the formation of this DNA secondary structure, indicating that G-quadruplexes are positively selected within pac1 in the evolution of herpesviruses...
March 1, 2018: ACS Infectious Diseases
F Berardinelli, A Sgura, A Facoetti, S Leone, B Vischioni, M Ciocca, A Antoccia
The pentacyclic acridine RHPS4 is a highly potent and specific G-quadruplex (G4) ligand, which binds and stabilizes telomeric G4 leading to the block of the replication forks at telomeres and consequently to telomere dysfunctionalization. In turn, the cell recognizes unprotected telomeres as DNA double-strand breaks with consequent activation of DNA repair response at telomeres, cellular growth impairment and death. Data from the literature showed the capability of this compound to sensitize U251MG glioblastoma radioresistant cell line to X-rays sparsely ionizing radiations...
February 27, 2018: FEBS Journal
David R Calabrese, Katherine Zlotkowski, Stephanie Alden, William M Hewitt, Colleen M Connelly, Robert M Wilson, Snehal Gaikwad, Lu Chen, Rajarshi Guha, Craig J Thomas, Beverly A Mock, John S Schneekloth
Approaches to characterize the nucleic acid-binding properties of drugs and druglike small molecules are crucial to understanding the behavior of these compounds in cellular systems. Here, we use a Small Molecule Microarray (SMM) profiling approach to identify the preferential interaction between chlorhexidine, a widely used oral antiseptic, and the G-quadruplex (G4) structure in the KRAS oncogene promoter. The interaction of chlorhexidine and related drugs to the KRAS G4 is evaluated using multiple biophysical methods, including thermal melt, fluorescence titration and surface plasmon resonance (SPR) assays...
February 22, 2018: Nucleic Acids Research
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