Recently, nucleic acid secondary structures, G-quadruplexes in particular, have received much attention. G-quadruplexes are non-canonical nucleic acid secondary structures that are formed from G-rich sequences. These sequences consist of four stretches of G residues (each stretch with two or more G residues) interspersed by sequences of variable composition that form the loops. The formation of G-quadruplexes is induced and stabilized by monovalent cations like potassium and sodium. The presence of G-quadruplexes was first reported in telomeres and subsequently in the promoter region of several genes, 5′UTR (untranslated regions) and 3′UTRs [1-6]. G-quadruplexes function as regulatory elements and can influence key biological processes including transcription [3], translation [4] and splicing [7]. Recently, G-quadruplexes were also reported to be enriched at certain positions of eukaryotic retrotransposons, which correspond to regulatory regions of genes and viruses [8, 9]. Genome-wide ...
G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets of guanine bases, can be highly stable and have been demonstrated to occur in vivo in the DNA of human cells and other systems, where they play important biological roles, influencing processes such as telomere maintenance, DNA replication and transcription, or in the case of RNA G-quadruplexes, RNA translation and processing. We report for the first time that DNA G-quadruplexes can be detected in the nuclei of the malaria parasite Plasmodium falciparum, which has one of the most A/T-biased genomes sequenced and therefore possesses few guanine-rich sequences with the potential to form G-quadruplexes ...
TY - JOUR. T1 - Repression of translation of human estrogen receptor α by G-quadruplex formation. AU - Balkwill, Graham D.. AU - Derecka, Kamila. AU - Garner, Thomas P.. AU - Hodgman, Charlie. AU - Flint, A. P F. AU - Searle, Mark S.. PY - 2009/12/8. Y1 - 2009/12/8. N2 - Tissue-specific expression of the human estrogen receptor α gene (ESR1) is achieved through multiple promoter sequences resulting in various mRNA transcripts encoding a common protein but differing in their 5′-untranslated region (5′-UTR). Many cancers are estrogen-sensitive with neoplastic growth stimulated through the estrogen receptor, a transcription factor that regulates developmental genes. We demonstrate that the human ESR1 gene is rich in potential quadruplex-forming sequences with 3 of 20 identified within exonic regions. In particular,we show using CD, UV, and NMR spectroscopy that a stable DNAG-quadruplex motif is formed within the exon C gene sequence. This motif, which PCR shows is transcribed in normal and ...
Electrochemical behavior of the anticancer doxorubicin hydrochloride( DOX) and the interaction of DOX with human telomere DNA were investigated by cyclic voltammetry in aqueous medium using p H 6. 0 PBS buffer. The results showed that a pair of reversible oxidation- reduction peaks were observed at- 0. 585 V and- 0. 638 V in p H 6. 0 PBS buffer. There existed excellent linearities between oxidation peak current and concentration of DOX in the ranges of 0. 03- 0. 8 μmol/L and0. 8- 10 μmol/L by linear sweep voltammetric method. Detection limit( S/N = 3) was 0. 01 μmol /L. The relative standard deviations of the oxidation peak current obtained from 11 determinations of the same solutions containing 0. 5 μmol/L DOX were 3. 5%. The oxidation peak current of DOX gradually decreased with the adding of various concentrations of human telomere DNA,due to interaction of DOX with human telomere DNA. The binding ratio was calculated to be 1 ∶ 1 and the binding equilibrium constant was 1. 11 × 103 L/mol.
G-Quadruplex (G4) structures of a human telomeric 24-mer (5′-TTAGGGTTAGGGTTAGGGTTAGGG-3′) sequence (Tel24) stabilized by sodium and potassium ions have been assessed using surface-enhanced Raman scattering (SERS) spectroscopy. The distinctive SERS spectra of Tel24 in the presence of 100 mM Na+ and 100 mM K+ were obtained and the SERS bands characteristic of the antiparallel baskettype and the mixed hybrid (3+1) structures, respectively, were identified and assigned. The influence of the SERS - active substrate on the scattering enhancement was studied using citrate- and chloride-covered silver nanoparticles, in the absence and presence of the aggregating agent (0.1 M Na2SO4 and 0.1 M K2SO4). The highly reproducible SERS spectra of Tel24 obtained in various SERS active media indicated the same adsorption mechanism of the cation - stabilized G-quadruplexes onto the metal surface, regardless of the silver colloid. The remarkable resemblance between the circular dichroism (CD) spectra of the ...
Telomeric DNA present at the ends of chromosomes in normal somatic cells is progressively shortened after each cell replication, which eventually triggers cell death. In contrast, the length of telomeric DNA in cancer cells is maintained by over-expressed telomerase, a reverse transcriptase, making cancer cells immortal. Due to this apparent difference, telomerase has recently emerged as an attractive target for cancer intervention. One of the efficient approaches to inhibit the telomerase activity is to induce G-quadruplex formation in the telomeric DNA regions by small molecules to block the binding of telomerase. Such small molecules, known as G-quadruplex binding ligands, are being developed as potential anti-cancer drugs.
Mounting evidence supports the presence of biologically relevant G-quadruplexes in single-cell organisms, but the existence of endogenous G-quadruplex structures in mammalian cells remains highly controversial. This is due, in part, to the common misconception that DNA and RNA molecules are passive information carriers with relatively little structural or functional complexity. For those working in the field, however, the lack of available tools for characterizing DNA structures in vivo remains a major limitation to addressing fundamental questions about structure-function relationships of nucleic acids. In this review, we present progress towards the direct detection of G-quadruplex structures by using small molecules and modified oligonucleotides as fluorescent probes. While most development has focused on cell-permeable probes that selectively bind to G-quadruplex structures with high affinity, these same probes can induce G-quadruplex folding, thereby making the native conformation of the ...
A significant part of eukaryotic genomes is formed by transposable elements (TEs) containing not only genes but also regulatory sequences. Some of the regulatory sequences located within TEs can form secondary structures like hairpins or three-stranded (triplex DNA) and four-stranded (quadruplex DNA) conformations. This review focuses on recent evidence showing that G-quadruplex-forming sequences in particular are often present in specific parts of TEs in plants and humans. We discuss the potential role of these structures in the TE life cycle as well as the impact of G-quadruplexes on replication, transcription, translation, chromatin status, and recombination. The aim of this review is to emphasize that TEs may serve as vehicles for the genomic spread of G-quadruplexes. These non-canonical DNA structures and their conformational switches may constitute another regulatory system that, together with small and long non-coding RNA molecules and proteins, contribute to the complex cellular network ...
For the development of K(+)-responsive RNA aptamers, we proposed a new general strategy that makes use of a G-quadruplex formation in response to K(+). This is the first report of developing an RNA aptamer that demonstrates ON/OFF switching of its target-binding activity by sensing the addition/removal of K(+).. ...
In human mitochondria the transcription machinery generates the RNA primers needed for initiation of DNA replication. A critical feature of the leading-strand origin of mitochondrial DNA replication is a CG-rich element denoted conserved sequence block II (CSB II). During transcription of CSB II, a G-quadruplex structure forms in the nascent RNA, which stimulates transcription termination and primer formation. Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. We here demonstrate that the unusual behavior of the RNA primer is explained by the formation of a stable G-quadruplex structure, involving the CSB II region in both the nascent RNA and the non-template DNA strand. Based on our data, we suggest that G-quadruplex formation between nascent RNA and the non-template DNA strand may be a regulated event, which decides the fate of RNA primers and ultimately the rate of initiation of DNA
Guanine-rich DNA sequences tend to form four-stranded G-quadruplex structures. Characteristic glycosidic conformational patterns along the G-strands, such as the 5-syn-anti-syn-anti pattern observed with the Oxytricha nova telomeric G-quadruplexes, have been well documented. However, an explanation for these featured glycosidic patterns has not emerged. This work presents MD simulation and free energetic analyses for simplified two-quartet [d(GG)](4) models and suggests that the four base pair step patterns show quite different relative stabilities: syn-anti , anti-anti , anti-syn , syn-syn. This suggests the following rule: when folding, anti-parallel G-quadruplexes tend to maximize the number of syn-anti steps and avoid the unfavorable anti-syn and syn-syn steps. This rule is consistent with most of the anti-parallel G-quadruplex structures in the Protein Databank (PDB). Structural polymorphisms of G-quadruplexes relate to these glycosidic conformational patterns and the lengths of the ...
Aggregation, red-NIR emission and light-up upon nucleic acid G-quadruplex binding have been investigated for a prototype core-extended naphthalene diimide, which is capable of fast cellular entry and nucleolar localization. Both high-level colocalization with an anti-G-quadruplex antibody and nucleolin displ
Some sequences of DNA that possess certain guanine or cytosine-riched stretches are capable of associating into four-stranded DNA structures, namely G-quadruplex and i-motif respectively. It has been suggested that some of these quadruplex structures could exist in some biologically important regions of DNA such as at the end of chromosomes and in the regulatory regions of oncogenes. In addition, due to their distinctive structural characteristics, quadruplex structures of DNA have been widely used as building blocks in various nanotechnological applications. With the aim of exploring new properties and applications of quadruplex DNA, we have (1) constructed i-motif DNA-based molecular devices that are operable through variations of their surrounding pH values; (2) developed certain fluorescence-tagged circular G-quadruplexes to be used as molecular probes; and (3) investigated the factors that affect the G-quadruplex that could undergo self-cleavage reactions. Finally, we have designed and ...
G-quadruplexes are nucleic acids structures stabilized by physiological concentration of potassium ions. Because low stability G-quadruplexes are hardly detectable by mass spectrometry, we optimized solvent conditions: isopropanol in a triethylamine/hexafluoroisopropanol mixture highly increased G-quadruplex sensitivity with no modification of the physiological G-quadruplex conformation.
Citation data is made available by participants Crossrefs Cited-by Linking service.. INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 80 PYRROLIZIDINE ALKALOIDS This report contains collective views of international .... ScienceDirect is worlds leading source scientific, technical, and medical research. Explore journals, books and articles.. Browse through 14,324,115 journal and book articles ScienceDirect.com. Role of Benzodioxole Group Interactions between Natural Alkaloids Chelerythrine and Coptisine and Human Telomeric G-Quadruplex DNA.. A tannin (or tannoid) is astringent, polyphenolic biomolecule binds and precipitates proteins and various other organic compounds including amino acids and ...
In this study we have used two fluorescent probes, tetrakis(diisopropylguanidino)-zinc-phthalocyanine (Zn-DIGP) and N-methylmesoporphyrin IX (NMM), to monitor the reassembly of "split" G-quadruplex probes on hybridization with an arbitrary "target" DNA. According to this approach, each split probe is designed to contain half of a G-quadruplex-forming sequence fused to a variable sequence that is complementary to the target DNA. Upon mixing the individual components, both base-pairing interactions and G-quadruplex fragment reassembly result in a duplex-quadruplex three-way junction that can bind to fluorescent dyes in a G-quadruplex-specific way. The overall fluorescence intensities of the resulting complexes were dependent on the formation of proper base-pairing interactions in the duplex regions, and on the exact identity of the fluorescent probe. Compared with samples lacking any "target" DNA, the fluorescence intensities of Zn-DIGP-containing samples were lower, and the fluorescence ...
The detection of biomarkers is of great significance in the diagnosis of numerous diseases, especially cancer. Herein, we developed a sensitive and universal fluorescent aptasensor strategy based on magnetic beads, DNA G-quadruplex, and exonuclease Ⅲ (Exo Ⅲ). In the presence of a target protein, a label-free single strand DNA (ssDNA) hybridized with the aptamer was released as a trigger DNA due to specific recognition between the aptamer and target. Subsequently, ssDNA initiates the Exo Ⅲ-aided recycling to amplify the fluorescence signal, which was caused by N-methylmesoporphyrin Ⅸ (NMM) insertion into the G-quadruplex structure. This proposed strategy combines the excellent specificity between the aptamer and target, high sensitivity of the fluorescence signal by G-quadruplex and Exo Ⅲaided recycling amplification. We selected (50-1200 nmol/L) MUC1, a common tumor biomarker, as the proof-of-concept target to test the specificity of our aptasensor. Results reveal that the sensor ...
Despite often being referred to as the inactive storage medium of genetic information DNA is of very dynamic and polymorphic nature adopting a variety of alternative secondary structures. In particular evidence for G-quadruplexes (GQPs), four-stranded helical complexes that are assembled from multiple stacked guanine tetrads, as important components in cellular processes has been increasing in recent years. These transiently formed alternative DNA structures have been shown to perform regulative roles in close to all integral biological processes such as recombination, replication, transcription and translation. In addition their polymorphic structure and high stability makes them attractive building blocks to be used in DNA nanoarchitectures and nanodevices.,br /,,br /,In the first part of this thesis the GQP folding properties of the DNA sequence (G,sub,4,/sub,CT),sub,3,/sub,G,sub,4,/sub, were characterized. The G-rich sequence was recently identified as a potential quadruplex-forming sequence ...
The Cover. cDNA microarray analysis of HeLa S3 cells treated with the G-quadruplex-interactive cationic porphyrin TMPyP4. Cells were treated with 100 µm TMPyP4 for 48 h, and mRNA was used to probe a 500-gene array. The expression of a number of oncogenes, including c-FOS, JUN-B, c-MYB, STAT-1, and c-MYC, was decreased specifically by this agent, and not by its positional isomer TMPyP2, which interacts with G-quadruplex DNA very poorly. The c-MYC oncogene is one of the most consistently down-regulated genes in this study and bears a sequence in its promoter that forms a G-quadruplex structure in vitro. For details, see 565 in this issue. ...
The hypoxia-inducible transcription factor (HIF) co-ordinates the response of tumours to low oxygen by stimulating genes involved in metabolism and angiogenesis. HIF pathway activation is associated with decreased progression-free survival and increased mortality; compounds that target this pathway are potential agents for the treatment of a range of solid tumour malignancies. Renal cancers are likely to be particularly sensitive to inhibition of the HIF pathway since ~80% show constitutive activation of HIF. We have previously described the di-substituted naphthalene derivative, CL67, which binds to a G-quadruplex higher-order structure in the HIF promoter sequence in vitro. We show here that CL67 blocks HIF expression leading to inhibition of HIF-transactivation and down-regulation of downstream target genes and proteins in renal carcinoma cell lines and in a mouse xenograft model of renal cancer. This inhibition is independent of pathways that control HIF abundance through oxygen-dependant ...
These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure ...
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BioAssay record AID 664269 submitted by ChEMBL: Binding affinity to c-myc quadruplex DNA FPu18T assessed as change in melting temperature at 2 uM by FRET-melting assay.
She received her Ph.D in 2006 from the University of Witten Herdecke. During her thesis she shed light on the question how of telomere binding proteins regulate G-quadruplex (G4) structures during the cell cycle. This work was done under the supervision of Prof. Dr. Hans-J Lipps und Dr. Daniela Rhodes. She subsequently did her postdoctorate research at Princeton University with Prof. Dr. Virginia Zakian where she studied the role of Pif1 helicase at G-quadruplex DNA structures during DNA replication. Currently in her lab she uses S. cerevisiae and human cell lines to understand the biological function of G-quadruplex structures and how this is connected to genome stability. ...
Abstract: DNA G-hairpins are potential key structures participating in folding of human telomeric guanine quadruplexes (GQ). We examined their properties by standard MD simulations starting from the folded state and long T-REMD starting from the unfolded state, accumulating ~130 {\mu}s of atomistic simulations. Antiparallel G-hairpins should spontaneously form in all stages of the folding to support lateral and diagonal loops, with sub-{\mu}s scale rearrangements between them. We found no clear predisposition for direct folding into specific GQ topologies with specific syn/anti patterns. Our key prediction stemming from the T-REMD is that an ideal unfolded ensemble of the full GQ sequence populates all 4096 syn/anti combinations of its four G-stretches. The simulations can propose idealized folding pathways but we explain that such few-state pathways may be misleading. In the context of the available experimental data, the simulations strongly suggest that the GQ folding could be best understood ...
TY - JOUR. T1 - Naphthalene diimide-derivatives G-quadruplex ligands induce cell proliferation inhibition, mild telomeric dysfunction and cell cycle perturbation in U251MG glioma cells. AU - Muoio, Daniela. AU - Berardinelli, Francesco. AU - Leone, Stefano. AU - Coluzzi, Elisa. AU - di Masi, Alessandra. AU - Doria, Filippo. AU - Freccero, Mauro. AU - Sgura, Antonella. AU - Folini, Marco. AU - Antoccia, Antonio. N1 - © 2018 Federation of European Biochemical Societies.. PY - 2018/10. Y1 - 2018/10. N2 - In the present paper, the biological effects of three different naphthalene diimides (NDIs) G-quadruplex (G4) ligands (H-NDI-Tyr, H-NDI-NMe2, and tetra-NDI-NMe2) were comparatively evaluated to those exerted by RHPS4, a well-characterized telomeric G4-ligand, in an in vitro model of glioblastoma. Data indicated that NDIs were very effective in blocking cell proliferation at nanomolar concentrations, although displaying a lower specificity for telomere targeting compared to RHPS4. In addition, ...
Both Pb2+ and Ba2+ can bind with high affinity to some specific DNA sequences, inducing the formation of unimolecular G-quadruplex structures. Trans location of a DNA probe containing such sequences through an alpha-hemolysin nanopore in the presence of Pb2+ or Ba2+ . would result in much prolonged DNA translocation events. Quantification of these events can reveal the concentrations of Pb2+ or Ba2+ at as low as 0.8 nM. Besides, Pb2+ and Ba2+ in the solution can be simultaneously detected and individually identified. Furthermore, the probe is highly selective for Pb2+ and Ba2+ detection without interference from other metal ions. This sensing strategy can be extended to many other analytes which can bind to DNA molecules with high affinity ...
G-quadruplexes, (non-canonical secondary structures), have gained recognition as viable targets for chemotherapeutic drug design based on their ability to interfere with cancer cell proliferation. These DNA structures, held together by Hoogsteen hydrogen
GTX1/4 can induce the formation of an antiparallel G-quadruplex structure in aptamer GO18-T-d and combine steadily in the groove at the top of the G-quadruplex structure. The complex structures and special induced fit mechanism between aptamer and small molecules provide a reference for aptamer development i
Our genome contains over 300,000 evolutionary conserved sequences that conform to the G4 consensus sequence (Fig 1A) (Huppert & Balasubramanian, 2005; Todd et al, 2005). G‐quadruplex structures have been suggested to play a role in several biological processes such as telomere maintenance (Maiti, 2010), gene regulation (Siddiqui‐Jain et al, 2002), DNA replication initiation (Besnard et al, 2012; Cayrou et al, 2012; Valton et al, 2014), epigenetic regulation (Sarkies et al, 2010), and gene conversion (Cahoon & Seifert, 2009). However, which and how many of the G4 sequences present in the genome form a G‐quadruplex structure at a given time in a human cell is not known. Nevertheless, a number of recent studies using fluorescently tagged G4 ligands (Rodriguez et al, 2012) and highly specific G4 antibodies (Biffi et al, 2013; Henderson et al, 2013) provide evidence that these structures are abundantly present in proliferating human cells. The assembly and disassembly of G‐quadruplex ...
The ability of compounds BMSG-SH-3-5 to stabilize telomeric G-quadruplexes has been demonstrated in previous studies using FRET, surface plasmon resonance, and circular dichroism techniques (Cuenca et al., 2008; Hampel et al., 2010). They are also confirmed to be inhibitors of the telomerase enzyme (Greulich-Bode K, unpublished observations). The present study shows that they are able to stabilize G-quadruplexes in promoter regions of the oncogenes c-kit and hif-1α, as well as a quadruplex formed in the mRNA of the bcl-2 gene. This gives them the potential to inhibit transcription and translation of these oncogenes or cell-survival genes, which may have antiproliferative or anticancer effects. Investigation of transcription or translation inhibition is beyond the scope of this study, although it is notable that we previously showed BMSG-SH-5 (Gunaratnam et al., 2011) to bind to a promoter quadruplex in the HSP90 gene and also to downregulate the expression of the HSP90 protein in ...
Our lab has developed an antibody specific for G-quadruplexes (BG4), which is commercially available.. BG4 is a highly specific monoclonal antibody that targets DNA G-quadruplex structures and has been tested in and ELISA, ChIP-seq, and immunocytochemistry.. The antibody construct (scFv, FLAG-tagged), that is the same as that published by us (Biffi et al., Nature Chem., 2013, Biffi et al., Nature Chem., 2014, Biffi et al., PLos ONE, 2014,) is commercially available:. http://www.merckmillipore.com/GB/en/product/Anti-DNA-G-quadruplex-structures-Antibody-clone-BG4,MM_NF-MABE917. http://www.merckmillipore.com/GB/en/product/Anti-DNA-G-quadruplex-structures-Antibody-clone-BG4,MM_NF-MABE917-25UL. The plasmid for BG4 (scFv) is also available:. https://www.addgene.org/55756/. Our recommended procedure for the expression and purification of BG4 from plasmid can be found in the attached document, which also includes a vector map:. See procedure. Our recommended protocol for the use of BG4 in ...
2N21: Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex.
Intercalated Motif (i-Motif) DNA structures may be formed in regions rich in 2-deoxyCytidine. Especially at acidic pH, these structures could be described as C-Quadruplexes with two parallel stranded sequences also held together in an antiparallel orientation by cytosine-cytosine base pairs. Since these structures are stable at acidic pH, they can act as nanoswitches by change in pH. As they were not considered to be stable at physiological pH, they were not initially considered to be relevant to biological systems. However, the stability of the cytosine-cytosine base pair is enhanced by intercallating ligands and so a variety of i-Motif structures are now considered to be biologically significant. Since i-Motif structures have now been observed forming and dissolving in living cells, these structures are now the subject of active investigation of the meaning of their activity in human cells. Research is also being directed to the effect of common DNA lesions, like depurinated sites, 8-oxo-dG ...
Zuschriften DOI: 10.1002/ange.201103422 G-Quadruplexes An Acyclic Oligoheteroaryle That Discriminates Strongly between Diverse G-Quadruplex Topologies** Florian Hamon, Eric Largy, Aurore Gudin-Beaurepaire, Myriam Rouchon-Dagois, Assitan Sidibe, David Monchaud, Jean-Louis Mergny, Jean-Francois Riou, Chi-Hung Nguyen, and Marie-Paule Teulade-Fichou* Quadruplex nucleic acids are secondary structures that may form in sequences containing guanine repeats.[1] These structures are strongly suspected to interfere with the transfer and the maintenance of the genetic information and therefore are the focus of considerable attention.[2] Quadruplexes may accommodate small synthetic compounds that could be used as probes to decipher their functions or as pharmacological agents to block various vital functions at the level of DNA or RNA.[3] These synthetic ligands should fulfill an essential requirement to enable correlating their in cellulo biological effects to their quadruplex recognition ability, namely ...
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Chemical structures of G-quartets and quadruplexes. (A) Anticonformation (top left) and syn conformation (top right) of guanosine. (B) Inosine (left) and 7-deaz
Antitumor properties of the potent G‐quadruplex ligand 3,11‐difluoro‐6,8, 13‐trimethyl‐8H‐quino[4,3,2‐kl]acridinium methosulfate (RHPS4) are driven by telomere uncapping events. RHPS4 has good selectivity for quadruplex DNA over duplex DNA as measured by surface plasmon resonance (Kquad 1.1 × 107 M−1); Kdup 3.4 × 105 M−1). In preclinical models of solid tumor xenografts RHPS4 potentiates the activity of camptothecins but good response is dependent on the timing of the drug sequence employed. These experiments teach how an agent of this novel class might be used clinically in combination with chemotherapeutic agents. Although RHPS4 has several drug‐like qualities (synthetic accessibility, water solubility, cellular uptake), a preliminary toxicological study revealed that the compound is a potent hERG inhibitor (IC50 0.2 M) and has additional receptor interactions, notably with muscarinic M1, M2 and M3 receptors. In an anaesthetized guinea pig cardiac model RHPS4 increased ...
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Daily News How Gaining and Losing Weight Affects the Body Millions of measurements from 23 people who consumed extra calories every day for a month reveal changes in proteins, metabolites, and gut microbiota that accompany shifts in body mass.. ...
Pneumococcus DNA, of weight-average molecular weight 1.6 million by light scattering, had a weight-average length of 4300 A by electron microscopy. Thus, the average mass per unit length was 370 molecular-weight units per A, or approximately two times that expected (208) for a Watson-Crick double helix. This corresponds to an average of 3.6 strands per molecule, which is close to that obtained by other methods. Morphologically, all the particles in the micrographs were relatively stiff, and had a cross-sectional height of 20 to 30 A. Some divided into two stiff branches of the same height, apparently double helical. Where the branches combined into one (minimally four-stranded) structure they apparently lay side by side in close association.. ...
Mise jour, larticle date de septembre 2015 AS1411 is a quadruplex-forming DNA oligonucleotide that functions as an aptamer to target nucleolin, a protein pre
BG4 is an engineered, structure-specific antibody probe that binds with high selectivity and low nanomolar affinity to DNA G-quadruplex structures
RNA Helicase associated with AU-rich element (RHAU) (DHX36) is a DEAH (Aspartic acid, Glumatic Acid, Alanine, Histidine)-package RNA helicase that can bind and unwind G4-quadruplexes in DNA and RNA. the microRNA machinery is definitely supported by related and nonadditive raises in PITX1 protein manifestation on Dicer and combined RHAU/Dicer knockdown. We also demonstrate a requirement of argonaute-2, a key RNA-induced silencing complex component, to mediate RHAU-dependent changes in PITX1 protein levels. These results demonstrate a novel part for RHAU in microRNA-mediated translational rules at a quadruplex-containing 3-untranslated region. Intro Guanine-rich nucleic acids are prone to fold into unique structures. ...
1PGZ: Structure-based incorporation of 6-methyl-8-(2-deoxy-beta-ribofuranosyl)isoxanthopteridine into the human telomeric repeat DNA as a probe for UP1 binding and destabilization of G-tetrad structures
A relatively new area of interest concerns the HS1.2 region of immunoglobulin. Although this region is not active in Ig production, it is conserved and several DNA regions have been shown to interact with specific proteins, thus suggesting a functional/regulative role for this region. In collaboration with prof. D. Frezza (University of Rome Tor Vergata) and prof. A. Pastore (Kings College of London, UK), we have shown that some DNA sequences belonging to the promotor regions with which these proteins interact can form an intramolecular quadruplex structure (Figure 3). Quadruplex DNA is not found only at telomeric edge of chromosomes but it is also frequently found in regulative regions of DNA. Thus, our studies suggest a functional, still unknown, role for this region. The solution structure of these structures is planned for the future ...
G-quadruplexes (G4) are stacked non-canonical nucleic acid structures found in specific G-rich DNA or RNA sequences in the human genome. G4 structures are liable for various biological functions; transcription, translation, cell aging as well as diseases such as cancer. These structures are therefore considered as important targets for the development of anticancer agents. Small organic heterocyclic molecules are well known to target and stabilize G4 structures. In this article, we have designed and synthesized 2,6-di-(4-carbamoyl-2-quinolyl)pyridine derivatives and their ability to stabilize G4-structures have been determined through the FRET melting assay. It has been established that these ligands are selective for G4 over duplexes and show a preference for the parallel conformation. Next, telomerase inhibition ability has been assessed using three cell lines (K562, MyLa and MV-4-11) and telomerase activity is no longer detected at 0.1 μM concentration for the most potent ligand 1c. The most
Recommended Articles:. Broyde, S., L. Wang, O. Rechkoblit, N. E. Geacintov, and D. J. Patel. 2008. Lesion processing: High-fidelity versus lesion-bypass DNA polymerases. Trends in biochemical sciences 33, (5): 209-219. Patel, D. J., J. B. Ma, Y. R. Yuan, K. Ye, Y. Pei, V. Kuryavyi, L. Malinina, G. Meister, and T. Tuschl. 2006. Structural biology of RNA silencing and its functional implications. Cold Spring Harbor symposia on quantitative biology 71, : 81-93. Patel, D. J., A. T. Phan, and V. Kuryavyi. 2007. Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: Diverse higher order DNA and RNA targets for cancer therapeutics. Nucleic acids research 35, (22): 7429-7455. Serganov, A., L. Huang, and D. J. Patel. 2008. Structural insights into amino acid binding and gene control by a lysine riboswitch. Nature 455, (7217): 1263-1267. Taverna, S. D., H. Li, A. J. Ruthenburg, C. D. Allis, and D. J. Patel. 2007. How chromatin-binding modules interpret histone modifications: Lessons from ...
This post includes 33 articles divided by category as follows: GQ-Biology (GQB). 8 articles GQ-Cations (GQC). 1 article GQ-Methods (GQM). 5 articles GQ-Nano & Technology (GQNT). 9 articles GQ-Recognition (GQR). 5 articles GQ-Structure & Dynamics (GQSD). 2 articles GQ-Supramolecular (GQS). 3 articles _____________________________________ • GQ-Biology. Studies aimed at the discovery of GQs in living organisms and the elucidation of their role in biological processes. (putative quadruplex sequences in genomes; proteins…