共查询到20条相似文献,搜索用时 0 毫秒
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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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Prof. Masato Ikeda Masahiro Kamimura Yukiko Hayakawa Dr. Aya Shibata Prof. Yukio Kitade 《Chembiochem : a European journal of chemical biology》2016,17(14):1304-1307
Stimulus‐responsive biomolecules are attractive targets to understand biomolecule behaviour as well as to explore their therapeutic and diagnostic applications. We demonstrate that a reduction‐responsive cleavable group (chemically caged unit) introduced into the guanine ring enables modulation of the secondary structure transition of an oligonucleotide in a reduction‐responsive and traceless manner leaving the unmodified oligonucleotide of interest. This simple but robust strategy could yield a variety of stimuli‐responsive oligonucleotides. 相似文献
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Targeting the BCL2 Gene Promoter G‐Quadruplex with a New Class of Furopyridazinone‐Based Molecules 下载免费PDF全文
Dr. Jussara Amato Alessia Pagano Dr. Domenica Capasso Dr. Sonia Di Gaetano Dr. Mariateresa Giustiniano Prof. Ettore Novellino Prof. Antonio Randazzo Dr. Bruno Pagano 《ChemMedChem》2018,13(5):406-410
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Dr. Jonathan Dickerhoff Prof. Dr. Klaus Weisz 《Chembiochem : a European journal of chemical biology》2018,19(9):927-930
A (3+1)‐hybrid‐type G‐quadruplex was substituted within its central tetrad by a single 2′‐fluoro‐modified guanosine. Driven by the anti‐favoring nucleoside analogue, a novel quadruplex fold with inversion of a single G‐tract and conversion of a propeller loop into a lateral loop emerges. In addition, scalar couplings across hydrogen bonds demonstrate the formation of intra‐ and inter‐residual F ??? H8?C8 pseudo‐hydrogen bonds within the modified quadruplexes. Alternative folding can be rationalized by the impact of fluorine on intermediate species on the basis of a kinetic partitioning mechanism. Apparently, chemical or other environmental perturbations are able to redirect folding of a quadruplex, possibly modulating its regulatory role in physiological processes. 相似文献
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Andrea Funke Beatrice Karg Dr. Jonathan Dickerhoff Dr. Darko Balke Prof. Dr. Sabine Müller Prof. Dr. Klaus Weisz 《Chembiochem : a European journal of chemical biology》2018,19(5):505-512
Binding of an indoloquinoline derivative with an aminoalkyl side chain to a truncated sequence from the MYC promoter region was studied through isothermal titration calorimetry (ITC). The targeted MYC3 sequence lacks 3′‐flanking nucleotides and forms a monomeric parallel quadruplex (G4) with a blunt‐ended 3′‐outer tetrad under the solution conditions employed. Analysis of ITC isotherms reveals multiple binding equilibria with the initial formation of a 1:2 ligand/quadruplex complex. Evaluation of electrophoretic mobilities as well as NMR spectral data confirm ligand‐induced dimerization of MYC3 quadruplexes with the ligand sandwiched between the two 3′‐outer tetrads. Additional ligand molecules in excess bind to the 5′‐outer tetrads of the sandwich complex. Such a ligand‐promoted G4 dimerization may be exploited for the controlled assembly or disassembly of G4 aggregates to expand on present quadruplex‐based technologies. 相似文献
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Ana Rita Duarte Enrico Cadoni Dr. Ana S. Ressurreição Prof. Dr. Rui Moreira Prof. Dr. Alexandra Paulo 《ChemMedChem》2018,13(9):869-893
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. On the basis of the organization of their structural elements, G4 ligands can be divided into three major families: one, fused heteroaromatic polycyclic systems; two, macrocycles; three, 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 the diversity of the G4 loops and grooves. The rationale behind the design of a very comprehensive set of ligands, with particular focus on the structural features required for binding to G4, is discussed and combined with the corresponding biochemical/biological data to highlight key structure–G4 interaction relationships. Analysis of the data suggests that the shape of the ligand is the major factor behind the G4 stabilizing effect of the ligands. The information here critically reviewed will certainly contribute to the development of new and better G4 ligands with application either as therapeutics or probes. 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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Ligand‐Mediated G‐Quadruplex Induction in a Double‐Stranded DNA Context by Cyclic Imidazole/Lysine Polyamide 下载免费PDF全文
Sefan Asamitsu Yue Li Dr. Toshikazu Bando Prof. Hiroshi Sugiyama 《Chembiochem : a European journal of chemical biology》2016,17(14):1317-1322
G‐quadruplex (G4) DNA is often observed as a DNA secondary structure in guanine‐rich sequences, and is thought to be relevant to pharmacological and biological events. Therefore, G4 ligands have attracted great attention as potential anticancer therapies or in molecular probe applications. Here, we designed cyclic imidazole/lysine polyamide (cIKP) as a new class of G4 ligand. It was readily synthesized without time‐consuming column chromatography. cIKP selectively recognized particular G4 structures with low nanomolar affinity. Moreover, cIKP exhibited the ability to induce G4 formation of the promoter of G4‐containing DNA in the context of stable double‐stranded DNA (dsDNA) under molecular crowding conditions. This cIKP might be applicable as a molecular probe for the detection of potential G4‐forming sequences in dsDNA. 相似文献
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Double‐stranded DNA (dsDNA) as a catalytic species has been applied in various key asymmetric reactions. Compared with dsDNA, G‐quadruplex DNAs (G4DNAs) have unique conformational structures and versatile complexation properties, and act expectedly as hosts to recognize planar aromatic molecules through π–π stacking. Based on the specific recognition for small molecules, G4DNA‐based catalysts have been used to assist the catalytic function, and have been applied in asymmetric organic reactions.
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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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Fluorescent Dansyl‐Guanosine Conjugates that Bind c‐MYC Promoter G‐Quadruplex and Downregulate c‐MYC Expression 下载免费PDF全文
Y. Pavan Kumar Puja Saha Dhurjhoti Saha Irene Bessi Prof. Dr. Harald Schwalbe Dr. Shantanu Chowdhury Prof. Dr. Jyotirmayee Dash 《Chembiochem : a European journal of chemical biology》2016,17(5):388-393
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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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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