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排序方式: 共有1299条查询结果,搜索用时 15 毫秒
51.
Mathias B. Danielsen Dr. Chenguang Lou Jolanta Lisowiec-Wachnicka Prof. Anna Pasternak Per T. Jørgensen Prof. Jesper Wengel 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(6):1368-1379
Off-target effects remain a significant challenge in the therapeutic use of gapmer antisense oligonucleotides (AONs). Over the years various modifications have been synthesized and incorporated into AONs, however, precise control of RNase H-induced cleavage and target sequence selectivity has yet to be realized. Herein, the synthesis of the uracil and cytosine derivatives of a novel class of 2′-deoxy-2′-fluoro-3′-C-hydroxymethyl-β-d -lyxo-configured nucleotides has been accomplished and the target molecules have been incorporated into AONs. Experiments on exonuclease degradation showed improved nucleolytic stability relative to the unmodified control. Upon the introduction of one or two of the novel 2′-fluoro-3′-C-hydroxymethyl nucleotides as modifications in the gap region of a gapmer AON was associated with efficient RNase H-mediated cleavage of the RNA strand of the corresponding AON:RNA duplex. Notably, a tailored single cleavage event could be engineered depending on the positioning of a single modification. The effect of single mismatched base pairs was scanned along the full gap region demonstrating that the modification enables a remarkable specificity of RNase H cleavage. A cell-based model system was used to demonstrate the potential of gapmer AONs containing the novel modification to mediate gene silencing. 相似文献
52.
Force-constant-decayed anisotropic network model: An improved method for predicting RNA flexibility 下载免费PDF全文
Wei-Bu Wang 《中国物理 B》2022,31(6):68704-068704
RNA is an important biological macromolecule, which plays an irreplaceable role in many life activities. RNA functions are largely determined by its tertiary structure and the intrinsic dynamics encoded in the structure. Thus, how to effective extract structure-encoded dynamics is of great significance for understanding RNA functions. Anisotropic network model (ANM) is an efficient method to investigate macromolecular dynamical properties, which has been widely used in protein studies. However, the performance of the conventional ANM in describing RNA flexibility is not as good as that on proteins. In this study, we proposed a new approach, named force-constant-decayed anisotropic network model (fcd-ANM), to improve the performance in investigating the dynamical properties encoded in RNA structures. In fcd-ANM, nucleotide pairs in RNA structure were connected by springs and the force constant of springs was decayed exponentially based on the separation distance to describe the differences in the inter-nucleotide interaction strength. The performance of fcd-ANM in predicting RNA flexibility was evaluated using a non-redundant structure database composed of 51 RNAs. The results indicate that fcd-ANM significantly outperforms the conventional ANM in reproducing the experimental B-factors of nucleotides in RNA structures, and the Pearson correlation coefficient between the predicted and experimental nucleotide B-factors was distinctly improved by 21.05% compared to the conventional ANM. Fcd-ANM can serve as a more effective method for analysis of RNA dynamical properties. 相似文献
53.
de Frutos M Brasiles S Tavares P Raspaud E 《The European physical journal. E, Soft matter》2005,17(4):429-434
Bacterial viruses (bacteriophages) consist of nucleic acid protected by a protein envelope called capsid. At the start of infection, the phage genome is translocated into the bacterial cytoplasm. In vitro (and also in vivo), this DNA release can be triggered by binding a specific receptor protein to the phage tail. The force responsible for the release arises from energy stored in the capsid due to strong confinement of the DNA. We show that this force can be modified by adding molecules like spermine that affect DNA conformation. The tetravalent cation spermine can reduce the pressure inside the capsid and induce condensation of the released DNA. We examine the effect of spermine on DNA ejection from phage T5 by using light scattering and gel electrophoresis to measure the amount of DNA remaining in the capsid at the end of ejection. We discuss the results in terms of free energy minimization and we demonstrate that the presence of a DNA condensate outside the phage generates an additional force pulling passively on the DNA remaining inside the capsid. 相似文献
54.
Robert Willenbring 《Discrete Applied Mathematics》2009,157(7):1607-1614
We construct a permutation representation for RNA secondary structure. We also introduce some basic combinatorial statistics for RNA secondary structure and relate them to permutation statistics when appropriate. These statistics allow us to quantify some structural phenomena in RNA secondary structure. 相似文献
55.
W. Grüner R. Giegerich D. Strothmann C. Reidys J. Weber I. L. Hofacker P. F. Stadler P. Schuster 《Monatshefte für Chemie / Chemical Monthly》1996,127(4):355-374
Summary Global relations between RNA sequences and secondary structures are understood as mappings from sequence space into shape space. These mappings are investigated by exhaustive folding of allGC andAU sequences with chain lengths up to 30. The computed structural data are evaluated through exhaustive enumeration and used as an exact reference for testing analytical results derived from mathematical models and sampling based on statistical methods. Several new concepts of RNA sequence to secondary structure mappings are investigated, among them that ofneutral networks (being sets of sequences folding into the same structure). Exhaustive enumeration allows to test several previously suggested relations: the number of (minimum free energy) secondary structures as a function of the chain length as well as the frequency distribution of structures at constant chain length (commonly resulting in generalized forms ofZipf's law).
Analyse der Beziehungen zwischen RNA-Sequenzen und Sekundärstrukturen durch vollständige Faltung, 1. Mitt. Faltung, Neutrale Netzwerke
Zusammenfassung Die globalen Benziehungen zwischen RNA-Sequenzen und Sekundärstrukturen werden als Abbildungen aus einem Raum aller Sequenzen in einen Raum aller Strukturen aufgefaßt. Diese Abbildungen werden durch Falten aller binären Sequenzen desGC-undAU-Alphabets mit Kettenlängen bis zun=30 untersucht. Die berechneten Strukturdaten werden durch vollständiges Abzählen ausgewertet und als eine exakte Referenz zum Überprüfen analytischer Resultate aus mathematischen Modellen sowie zum Testen statistisch erhobener Proben verwendet. Einige neuartige Konzepte zur Beschreibung der Beziehungen zwischen Sequenzen und Strukturen werden eingehend untersucht, unter ihnen der Begriff derneutralen Netzwerke. Ein neutrales Netzwerk besteht aus allen Sequenzen, die eine bestimmte Struktur ausbilden. Vollständiges Abzählen ermöglicht beispielsweise die Bestimmung aller Strukturen minimaler freier Energie in Abhängigkeit von der Kettenlänge ebenso wie die Bestimmung der Häufigkeitsverteilungen der Strukturen bei konstanten Kettenlängen. Die letzteren folgen einer verallgemeinerten FormZipfschen Gesetzes.相似文献
56.
Elaina P. Boyle Dr. Levan Lomidze Prof. Dr. Karin Musier-Forsyth Prof. Dr. Besik Kankia 《ChemistryOpen》2022,11(2):e202100276
Nucleic acid quadruplexes are proposed to play a role in the regulation of gene expression, are often present in aptamers selected for specific binding functions and have potential applications in medicine and biotechnology. Therefore, understanding their structure and thermodynamic properties and designing highly stable quadruplexes is desirable for a variety of applications. Here, we evaluate DNA→RNA substitutions in the context of a monomolecular, antiparallel quadruplex, the thrombin-binding aptamer (TBA, GGTTGGTGTGGTTGG) in the presence of either K+ or Sr2+. TBA predominantly folds into a chair-type configuration containing two G-tetrads, with G residues in both syn and anti conformation. All chimeras with DNA→RNA substitutions (G→g) at G residues requiring the syn conformation demonstrated strong destabilization. In contrast, G→g substitutions at Gs with anti conformation increased stability without affecting the monomolecular chair-type topology. None of the DNA→RNA substitutions in loop positions affected the quadruplex topology; however, these substitutions varied widely in their stabilizing or destabilizing effects in an unpredictable manner. This analysis allowed us to design a chimeric DNA/RNA TBA construct that demonstrated substantially improved stability relative to the all-DNA construct. These results have implications for a variety of quadruplex-based applications including for the design of dynamic nanomachines. 相似文献
57.
Sung-Sik You Hyeong-Won Ryu Young Cho Dae-Young Kim Thong-Sung Ko 《Reaction Kinetics and Catalysis Letters》1999,66(1):121-126
The nonenzymatic hydrolysis of RNA by polyvinylpyrrolidone (PVP) has been investigated. A bell-shaped kinetics was observed
when the first order rate constant of the reaction was ploted as a function of PVP concentration, which means the kinetic
feature of PVP as a degradative receptor distinct from those of degradative enzymes (e.g., ribonuclease). 相似文献
58.
Toehold‐initiated Rolling Circle Amplification for Visualizing Individual MicroRNAs In Situ in Single Cells 下载免费PDF全文
Ruijie Deng Dr. Longhua Tang Qianqian Tian Dr. Ying Wang Lei Lin Prof. Dr. Jinghong Li 《Angewandte Chemie (International ed. in English)》2014,53(9):2389-2393
The ability to quantitate and visualize microRNAs (miRNAs) in situ in single cells would greatly facilitate the elucidation of miRNA‐mediated regulatory circuits and their disease associations. A toehold‐initiated strand‐displacement process was used to initiate rolling circle amplification of specific miRNAs, an approach that achieves both stringent recognition and in situ amplification of the target miRNA. This assay, termed toehold‐initiated rolling circle amplification (TIRCA), can be utilized to identify miRNAs at physiological temperature with high specificity and to visualize individual miRNAs in situ in single cells within 3 h. TIRCA is a competitive candidate technique for in situ miRNA imaging and may help us to understand the role of miRNAs in cellular processes and human diseases in more detail. 相似文献
59.
A Biocatalytic Cascade for Versatile One‐Pot Modification of mRNA Starting from Methionine Analogues 下载免费PDF全文
Fabian Muttach Prof. Dr. Andrea Rentmeister 《Angewandte Chemie (International ed. in English)》2016,55(5):1917-1920
Methyltransferases have proven useful to install functional groups site‐specifically in different classes of biomolecules when analogues of their cosubstrate S‐adenosyl‐l ‐methionine (AdoMet) are available. Methyltransferases have been used to address different classes of RNA molecules selectively and site‐specifically, which is indispensable for biophysical and mechanistic studies as well as labeling in the complex cellular environment. However, the AdoMet analogues are not cell‐permeable, thus preventing implementation of this strategy in cells. We present a two‐step enzymatic cascade for site‐specific mRNA modification starting from stable methionine analogues. Our approach combines the enzymatic synthesis of AdoMet with modification of the 5′ cap by a specific RNA methyltransferase in one pot. We demonstrate that a substrate panel including alkene, alkyne, and azido functionalities can be used and further derivatized in different types of click reactions. 相似文献
60.
Mark A. Boerneke Sergey M. Dibrov Thomas Hermann 《Angewandte Chemie (International ed. in English)》2016,55(12):4097-4100
RNA nanotechnology uses RNA structural motifs to build nanosized architectures that assemble through selective base‐pair interactions. Herein, we report the crystal‐structure‐guided design of highly stable RNA nanotriangles that self‐assemble cooperatively from short oligonucleotides. The crystal structure of an 81 nucleotide nanotriangle determined at 2.6 Å resolution reveals the so‐far smallest circularly closed nanoobject made entirely of double‐stranded RNA. The assembly of the nanotriangle architecture involved RNA corner motifs that were derived from ligand‐responsive RNA switches, which offer the opportunity to control self‐assembly and dissociation. 相似文献