共查询到20条相似文献,搜索用时 0 毫秒
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Prachi Agarwala Satyaprakash Pandey Dr. Souvik Maiti 《Chembiochem : a European journal of chemical biology》2013,14(16):2077-2081
With the potential to engineer biological systems, synthetic biology is an emerging field that combines various disciplines of sciences. It encompasses combinations of DNA, RNA and protein modules for constructing desired systems and the “rewiring” of existing signalling networks. Despite recent advances, this field still lags behind in the artificial reconstruction of cellular processes, and thus demands new modules and switches to create “genetic circuits”. The widely characterised noncanonical nucleic acid secondary structures, G‐quadruplexes are promising candidates to be used as biological modules in synthetic biology. Structural plasticity and functional versatility are significant G‐quadruplex traits for its integration into a biological system and for diverse applications in synthetic circuits. 相似文献
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Dr. Sebastian Müller Dr. Katta Laxmi‐Reddy Dr. Prakrit V. Jena Dr. Benoit Baptiste Dr. Zeyuan Dong Dr. Frédéric Godde Prof. Taekjip Ha Dr. Raphaël Rodriguez Prof. Shankar Balasubramanian Dr. Ivan Huc 《Chembiochem : a European journal of chemical biology》2014,15(17):2563-2570
We previously identified quinoline‐based oligoamide helical foldamers and a trimeric macrocycle as selective ligands of DNA quadruplexes. Their helical structures might permit targeting of the backbone loops and grooves of G‐quadruplexes instead of the G‐tetrads. Given the vast array of morphologies G‐quadruplex structures can adopt, this might be a way to achieve sequence selective binding. Here, we describe the design and synthesis of molecules based on macrocyclic and helically folded oligoamides. We tested their ability to interact with the human telomeric G‐quadruplex and an array of promoter G‐quadruplexes by using FRET melting assay and single‐molecule FRET. Our results show that they constitute very potent ligands—comparable to the best so far reported. Their modes of interaction differ from those of traditional tetrad binders, thus opening avenues for the development of molecules specific for certain G‐quadruplex conformations. 相似文献
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Indolo[3,2‐c]quinoline G‐Quadruplex Stabilizers: a Structural Analysis of Binding to the Human Telomeric G‐Quadruplex 下载免费PDF全文
Dr. João Lavrado Dr. Stephan A. Ohnmacht Dr. Isabel Correia Clara Leitão Sílvia Pisco Dr. Mekala Gunaratnam Prof. Rui Moreira Prof. Stephen Neidle Dr. Daniel J. V. A. dos Santos Dr. Alexandra Paulo 《ChemMedChem》2015,10(5):836-849
A library of 5‐methylindolo[3,2‐c]quinolones (IQc) with various substitution patterns of alkyldiamine side chains were evaluated for G‐quadruplex (G4) binding mode and efficiency. Fluorescence resonance energy transfer melting assays showed that IQcs with a positive charge in the heteroaromatic nucleus and two weakly basic side chains are potent and selective human telomeric (HT) and gene promoter G4 stabilizers. Spectroscopic studies with HT G4 as a model showed that an IQc stabilizing complex involves the binding of two IQc molecules (2,9‐bis{[3‐(diethylamino)propyl]amino}‐5‐methyl‐11H‐indolo[3,2‐c]quinolin‐5‐ium chloride, 3 d ) per G4 unit, in two non‐independent but equivalent binding sites. Molecular dynamics studies suggest that end‐stacking of 3 d induces a conformational rearrangement in the G4 structure, driving the binding of a second 3 d ligand to a G4 groove. Modeling studies also suggest that 3 d , with two three‐carbon side chains, has the appropriate geometry to participate in direct or water‐mediated hydrogen bonding to the phosphate backbone and/or G4 loops, assisted by the terminal nitrogen atoms of the side chains. Additionally, antiproliferative studies showed that IQc compounds 2 d (2‐{[3‐(diethylamino)propyl]amino}‐5‐methyl‐11H‐indolo[3,2‐c]quinolin‐5‐ium chloride) and 3 d are 7‐ to 12‐fold more selective for human malignant cell lines than for nonmalignant fibroblasts. 相似文献
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Higher‐Order Human Telomeric G‐Quadruplex DNA Metalloenzymes Enhance Enantioselectivity in the Diels–Alder Reaction 下载免费PDF全文
Yinghao Li Dr. Guoqing Jia Dr. Changhao Wang Mingpan Cheng Prof. Dr. Can Li 《Chembiochem : a European journal of chemical biology》2015,16(4):618-624
Short human telomeric (HT) DNA sequences form single G‐quadruplex (G4) units and exhibit structure‐based stereocontrol for a series of reactions. However, for more biologically relevant higher‐order HT G4‐DNAs (beyond a single G4 unit), the catalytic performances are unknown. Here, we found that higher‐order HT G4‐DNA copper metalloenzymes (two or three G4 units) afford remarkably higher enantioselectivity (>90 % ee) and a five‐ to sixfold rate increase, compared to a single G4 unit, for the Diels–Alder reaction. Electron paramagnetic resonance (EPR) and enzymatic kinetic studies revealed that the distinct catalytic function between single and higher‐order G4‐DNA copper metalloenzymes can be attributed to different CuII coordination environments and substrate specificity. Our finding suggests that, like protein enzymes and ribozymes, higher‐order structural organization is crucial for G4‐DNA‐based catalysis. 相似文献
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Inside Cover: Looking for Efficient G‐Quadruplex Ligands: Evidence for Selective Stabilizing Properties and Telomere Damage by Drug‐Like Molecules (ChemMedChem 4/2015) 下载免费PDF全文
Dr. Bruno Pagano Dr. Jussara Amato Nunzia Iaccarino Dr. Chiara Cingolani Dr. Pasquale Zizza Dr. Annamaria Biroccio Prof. Ettore Novellino Prof. Antonio Randazzo 《ChemMedChem》2015,10(4):586-586
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Looking for Efficient G‐Quadruplex Ligands: Evidence for Selective Stabilizing Properties and Telomere Damage by Drug‐Like Molecules 下载免费PDF全文
Dr. Bruno Pagano Dr. Jussara Amato Nunzia Iaccarino Dr. Chiara Cingolani Dr. Pasquale Zizza Dr. Annamaria Biroccio Prof. Ettore Novellino Prof. Antonio Randazzo 《ChemMedChem》2015,10(4):640-649
There is currently significant interest in the development of G‐quadruplex‐interactive compounds, given the relationship between the ability to stabilize these non‐canonical DNA structures and anticancer activity. In this study, a set of biophysical assays was applied to evaluate the binding of six drug‐like ligands to DNA G‐quadruplexes with different folding topologies. Interestingly, two of the investigated ligands showed selective G‐quadruplex‐stabilizing properties and biological activity. These compounds may represent useful leads for the development of more potent and selective ligands. 相似文献
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Masayuki Tera Keisuke Iida Hiromichi Ishizuka Motoki Takagi Dr. Masami Suganuma Dr. Takayuki Doi Prof. Dr. Kazuo Shin‐ya Dr. Kazuo Nagasawa Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(3):431-435
A novel G‐quadruplex binder , L1H1‐7OTD (shown in color by atom type), was developed. This macrocyclic heptaoxazole potently and selectively stabilizes telomeric DNA in an intramolecular antiparallel G‐quadruplex conformation. L1H1‐7OTD shows selective cytotoxicity toward HeLa cells, a telomerase‐positive cell line.
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Development of Fluorescent Protein Probes Specific for Parallel DNA and RNA G‐Quadruplexes 下载免费PDF全文
Dr. Dung Thanh Dang Prof. Dr. Anh Tuân Phan 《Chembiochem : a European journal of chemical biology》2016,17(1):42-45
We have developed fluorescent protein probes specific for parallel G‐quadruplexes by attaching cyan fluorescent protein to the G‐quadruplex‐binding motif of the RNA helicase RHAU. Fluorescent probes containing RHAU peptide fragments of different lengths were constructed, and their binding to G‐quadruplexes was characterized. The selective recognition and discrimination of G‐quadruplex topologies by the fluorescent protein probes was easily detected by the naked eye or by conventional gel imaging. 相似文献
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Dr. Antonella Virgilio Prof. Veronica Esposito Dr. Giuseppe Citarella Prof. Luciano Mayol Prof. Aldo Galeone 《Chembiochem : a European journal of chemical biology》2012,13(15):2219-2224
Several anti‐HIV aptamers adopt DNA quadruplex structures. Among these, “Hotoda's aptamer” (base sequence TGGGAG) was one of the first to be discovered. Although it has been the topic of some recent research, no detailed structural investigations have been reported. Here we report structural investigations on this aptamer and analogues with related sequences, by using UV, CD, and NMR spectroscopy as well as electrophoretic techniques. The addition of a 3′‐end thymine has allowed us to obtain a single, investigable quadruplex structure. Data clearly point to the presence of an A‐tetrad. Furthermore, the effects of the incorporation of an 8‐methyl‐2′‐deoxyguanosine at the 5′‐end of the G‐run were investigated. 相似文献
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Osman Doluca Prof. Dr. Alexandre S. Boutorine Dr. Vyacheslav V. Filichev 《Chembiochem : a European journal of chemical biology》2011,12(15):2365-2374
The majority of studies on DNA triple helices have been focused on pH‐sensitive parallel triplexes with Hoogsteen CT‐containing third strands that require protonation of cytosines. Reverse Hoogsteen GT/GA‐containing antiparallel triplex‐forming oligonucleotides (TFOs) do not require an acidic pH but their applicability in triplex technology is limited because of their tendency to form undesired highly stable aggregates such as G‐quadruplexes. In this study, G‐rich oligonucleotides containing 2–4 insertions of twisted intercalating nucleic acid (TINA) monomers are demonstrated to disrupt the formation of G‐quadruplexes and form stable antiparallel triplexes with target DNA duplexes. The structure of TINA‐incorporated oligonucleotides was optimized, the rules of their design were established and the optimal triplex‐forming oligonucleotides were selected. These oligonucleotides show high affinity towards a 16 bp homopurine model sequence from the HIV‐1 genome; dissociation constants as low as 160 nM are observed whereas the unmodified TFO does not show any triplex formation and instead forms an intermolecular G‐quadruplex with Tm exceeding 90 °C in the presence of 50 mM NaCl. Here we present a set of rules that help to reach the full potential of TINA‐TFOs and demonstrate the effect of TINA on the formation and stability of triple helical DNA. 相似文献
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Expanding the Potential of G‐Quadruplex Structures: Formation of a Heterochiral TBA Analogue 下载免费PDF全文
Dr. Antonella Virgilio Prof. Michela Varra Dr. Maria Scuotto Dr. Antonella Capuozzo Dr. Carlo Irace Prof. Luciano Mayol Dr. Veronica Esposito Prof. Aldo Galeone 《Chembiochem : a European journal of chemical biology》2014,15(5):652-655
In order to expand the potential applications of G‐quadruplex structures, we explored the ability of heterochiral oligodeoxynucleotides based on the thrombin‐binding aptamer (TBA) sequence to fold into similar complexes, with particular focus on their resistance in biological environments. A combination of CD and NMR techniques was used. Similarly to TBA, the ODN ggTTggtgtggTTgg (lower case letters indicate L residues) is able to fold into a chair‐like antiparallel G‐quadruplex structure, but has a slightly higher thermal stability. The discovery that heterochiral ODNs are able to form stable G‐quadruplex structures opens up new possibilities for their development in several fields, as aptamers, sensors and, as recently shown, as catalysts for enantioselective reactions. 相似文献
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The 5′‐AG5CC‐3′ Fragment from the Human CPEB3 Ribozyme Forms an Ultrastable Parallel RNA G‐Quadruplex 下载免费PDF全文
Katharina Kulikov Dr. Senada Nozinovic Dr. Stephanie Kath‐Schorr 《Chembiochem : a European journal of chemical biology》2017,18(11):969-973
An unusually thermostable G‐quadruplex is formed by a sequence fragment of a naturally occurring ribozyme, the human CPEB3 ribozyme. Strong evidence is provided for the formation of a uniquely stable intermolecular G‐quadruplex structure consisting of five tetrad layers, by using CD spectroscopy, UV melting curves, 2D NMR spectroscopy, and gel shift analysis. The cationic porphyrin TMPyP4 destabilizes the complex. 相似文献
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Dr. Valentina Casagrande Dr. Erica Salvati Dr. Antonello Alvino Dr. Alessandro Altieri Dr. Alina Ciammaichella Dr. Sara Iachettini Dr. Carlo Leonetti Prof. Giancarlo Ortaggi Dr. Manuela Porru Prof. Armandodoriano Bianco Dr. Annamaria Biroccio 《ChemMedChem》2012,7(12):2144-2154
Based on previous work on both perylene and coronene derivatives as G‐quadruplex binders, a novel chimeric compound was designed: N,N′‐bis[2‐(1‐piperidino)‐ethyl]‐1‐(1‐piperidinyl)‐6‐[2‐(1‐piperidino)‐ethyl]‐benzo[ghi]perylene‐3,4:9,10‐tetracarboxylic diimide (EMICORON), having one piperidinyl group bound to the perylene bay area (positions 1, 12 and 6, 7 of the aromatic core), sufficient to guarantee good selectivity, and an extended aromatic core able to increase the stacking interactions with the terminal tetrad of the G‐quadruplex. The obtained “chimera” molecule, EMICORON, rapidly triggers extensive DNA damage of telomeres, associated with the delocalization of telomeric protein protection of telomeres 1 (POT1), and efficiently limits the growth of both telomerase‐positive and ‐negative tumor cells. Notably, the biological effects of EMICORON are more potent than those of the previously described perylene derivative (PPL3C), and more interestingly, EMICORON appears to be detrimental to transformed and tumor cells, while normal fibroblasts expressing telomerase remain unaffected. These results identify a new promising G‐quadruplex ligand, structurally and biologically similar on one side to coronene and on the other side to a bay‐monosubstituted perylene, that warrants further studies. 相似文献