Synthesis and structure of fluoroindole nucleosides

2007 ◽  
Vol 85 (4) ◽  
pp. 283-292 ◽  
Author(s):  
Jelena Božilović ◽  
Jan W Bats ◽  
Joachim W Engels
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Driving Forces ◽  
Rna Stability ◽  
Building Blocks ◽  
Biologically Active ◽  
Dna And Rna ◽  
The Stability ◽  
Indole Synthesis

Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation, and to tune DNA and RNA hybridization conditions. Nucleoside analogues are chemical means to investigate hydrogen bonds, base stacking, and solvation as the three predominant forces that are responsible for the stability of nucleic acids. To obtain deeper insight into the contributions of these interactions to RNA stability, we decided to synthesize some novel nucleic acid analogues where the nucleobases are replaced by fluoroindoles. Fluorinated indoles can be compared with fluorinated benzimidazoles to determine the role of nitrogen in five-membered ring systems. The synthesis of fluoroindole ribonucleosides as well as the X-ray crystal structures of all synthesized fluoroindole ribonucleosides are reported here. These compounds could also be building blocks for a variety of biologically active RNA analogues.Key words: indoles, nucleosides, crystal structure, glycosilation, indole-synthesis.

scholarly journals Graphene Oxide: A Smart (Starting) Material for Natural Methylxanthines Adsorption and Detection

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4247 ◽  
Author(s):  
Rita Petrucci ◽  
Isabella Chiarotto ◽  
Leonardo Mattiello ◽  
Daniele Passeri ◽  
Marco Rossi ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Graphene Oxide ◽  
Nucleic Acids ◽  
Reduced Graphene Oxide ◽  
Electrochemical Sensors ◽  
Enzymatic Digestion ◽  
Biologically Active ◽  
Polar Solvents ◽  
Dna And Rna ◽  
Reduced Graphene

Natural methylxanthines, caffeine, theophylline and theobromine, are widespread biologically active alkaloids in human nutrition, found mainly in beverages (coffee, tea, cocoa, energy drinks, etc.). Their detection is thus of extreme importance, and many studies are devoted to this topic. During the last decade, graphene oxide (GO) and reduced graphene oxide (RGO) gained popularity as constituents of sensors (chemical, electrochemical and biosensors) for methylxanthines. The main advantages of GO and RGO with respect to graphene are the easiness and cheapness of synthesis, the notable higher solubility in polar solvents (water, among others), and the higher reactivity towards these targets (mainly due to – interactions); one of the main disadvantages is the lower electrical conductivity, especially when using them in electrochemical sensors. Nonetheless, their use in sensors is becoming more and more common, with the obtainment of very good results in terms of selectivity and sensitivity (up to 5.4 × 10−10 mol L−1 and 1.8 × 10−9 mol L−1 for caffeine and theophylline, respectively). Moreover, the ability of GO to protect DNA and RNA from enzymatic digestion renders it one of the best candidates for biosensors based on these nucleic acids. This is an up-to-date review of the use of GO and RGO in sensors.

An Investigation of the Anomalous Staining of Chromatin by the Acid Dyes, Methyl Blue and Aniline Blue

1962 ◽  
Vol s3-103 (64) ◽  
pp. 519-530
Author(s):  
R. B. McKAY
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Methyl Blue ◽  
Aniline Blue ◽  
Acid Dyes ◽  
Dna And Rna ◽  
Basic Dyes ◽  
Blue Stain ◽  
High Degree ◽  
Mechanism Of The Reaction

Methyl blue and aniline blue, though acid dyes, stain the chromatin of the spermatogenetic cells of the mouse (especially of the primary spermatocytes) strongly. Extraction of the basiphil nucleic acid constituents from the chromatin causes loss of this property, while destruction of acidophilia in the protein constituents does not. It has been concluded that the dyes interact with the nucleic acids. Further, they appear to react with both DNA and RNA in the chromatin, although they show no affinity for the cytoplasm of the exocrine cells in sections of pancreas, which is rich in RNA. The mechanism of the reaction has not been fully elucidated, although apparently the dyes do not behave as basic dyes towards the nucleic acids, and the interaction is non-ionic. Methyl blue and aniline blue stain strongly other ‘acidic’ substrates, such as cellulose and nitrocellulose, and attempts have been made to relate the staining of nucleic acids to the staining of these substrates, particularly cellulose; for the staining properties of this substrate have been intensively investigated elsewhere. No satisfactory correlation, however, has been obtained, for nitrocellulose has been found to be less strongly stained at pH 3.0 than at pH 7.1, while the reverse is true for cellulose. Further, only one of 3 direct cotton dyes used appears to have any affinity for the chromatin of the spermatogenetic cells. Direct cotton dyes have large flat molecules with a high degree of conjugation. It is suggested that these characteristics are essential for interaction with nucleic acids, and also that the molecule must be reasonably compact. Finally, it has been shown that methyl blue, aniline blue, and 3 direct cotton dyes of the azo type have no ability to stain the glycogen in liver cells, yet glycogen is very closely related to cellulose.

scholarly journals Viperin catalyzes methionine oxidation to promote protein expression and function of helicases

2019 ◽  
Vol 5 (8) ◽  
pp. eaax1031 ◽  
Author(s):  
Lei Bai ◽  
Jiazhen Dong ◽  
Zhenqiu Liu ◽  
Youliang Rao ◽  
Pinghui Feng ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Methionine Oxidation ◽  
Biological Processes ◽  
Loss Of Function ◽  
Rna Helicases ◽  
Dna And Rna ◽  
Biochemical Studies ◽  
The Stability ◽  
And Function

Helicases play pivotal roles in fundamental biological processes, and posttranslational modifications regulate the localization, function, and stability of helicases. Here, we report that methionine oxidation of representative helicases, including DNA and RNA helicases of viral (ORF44 of KSHV) and cellular (MCM7 and RIG-I) origin, promotes their expression and functions. Cellular viperin, a major antiviral interferon-stimulated gene whose functions beyond host defense remain largely unknown, catalyzes the methionine oxidation of these helicases. Moreover, biochemical studies entailing loss-of-function mutations of helicases and a pharmacological inhibitor interfering with lipid metabolism and, hence, decreasing viperin activity indicate that methionine oxidation potently increases the stability and enzyme activity of these helicases that are critical for DNA replication and immune activation. Our work uncovers a pivotal role of viperin in catalyzing the methionine oxidation of helicases that are implicated in diverse fundamental biological processes.

Analytical validation of an immune response assay for classifying solid tumors.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 68-68
Author(s):  
Jeff Conroy ◽  
Sean Glenn ◽  
Blake Burgher ◽  
Antonios Papanicolau-Sengos ◽  
Jonathan Andreas ◽  
...  
Keyword(s):  
Immune Response ◽  
Nucleic Acids ◽  
Solid Tumors ◽  
Checkpoint Inhibitors ◽  
Rna Stability ◽  
Analytical Performance ◽  
Rna Seq ◽  
Diagnostic Laboratory ◽  
Typical Sample ◽  
Dna And Rna

68 Background: An advanced diagnostic laboratory test (Immune Advance) was developed that analyzes multiple DNA and RNA biomarkers to predict the likelihood of response to checkpoint inhibitors in patients with solid tumors. Using RNA-seq and DNA-seq, the NGS test measures gene expression of immune response genes and overall mutational burden. The studies described here were designed to validate the analytical performance of the test on the Ion Torrent System in our CLIA lab. Methods: Studies were designed to characterize the analytical performance of an immune response NGS assay using total nucleic acids from >100 FFPE tissues representing NSCLC, melanoma, renal cell carcinoma, and bladder cancer. Performance variables with respect to gene-specific amplicon specificity, linearity, and limits of detection were estimated with various sample dilutions and input nucleic acids. The effects of the tumor micro-environment (adjacent benign tissue, necrosis) was evaluated by including these potential interferents in the assay. Analytical precision including intra-assay, inter-assay, and inter-operator reproducibility was measured by testing replicate FFPE tissue sections. Accuracy was determined by comparing select transcript and DNA level variants with those from established IHC, RT-PCR, and NGS assays. Transcript stability in FFPE specimens was evaluated in serial sections from blocks with routine storage and compared to originating matched fresh frozen specimens. Results: RNA stability was demonstrated by high degree of correlation between matched frozen and FFPE samples. Analytic precision was demonstrated by high correlation between RNA-Seq and TaqMan results for genes evaluated. As compared to IHC the results for RNA-Seq were continuous rather than bimodal and allowed for a much more detailed analysis of the immune response. Immune signatures were maintained with variable RNA/DNA input amounts, altered tumor micro-environments, and potential interferents demonstrating tolerance to typical sample types tested. Reproducibility results show little variation between runs and operators. Conclusions: The analytical performance of the Immune Advance assay has been validated for clinical use using FFPE tumor specimens.

scholarly journals Oligonucleotide-based systems: DNA, microRNAs, DNA/RNA aptamers

2016 ◽  
Vol 60 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Pawan Jolly ◽  
Pedro Estrela ◽  
Michael Ladomery
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Rna Aptamers ◽  
Locked Nucleic Acid ◽  
Synthetic Analogue ◽  
Dna And Rna ◽  
Naturally Occurring ◽  
Wide Range ◽  
Synthetic Oligonucleotides ◽  
Shed Light

There are an increasing number of applications that have been developed for oligonucleotide-based biosensing systems in genetics and biomedicine. Oligonucleotide-based biosensors are those where the probe to capture the analyte is a strand of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or a synthetic analogue of naturally occurring nucleic acids. This review will shed light on various types of nucleic acids such as DNA and RNA (particularly microRNAs), their role and their application in biosensing. It will also cover DNA/RNA aptamers, which can be used as bioreceptors for a wide range of targets such as proteins, small molecules, bacteria and even cells. It will also highlight how the invention of synthetic oligonucleotides such as peptide nucleic acid (PNA) or locked nucleic acid (LNA) has pushed the limits of molecular biology and biosensor development to new perspectives. These technologies are very promising albeit still in need of development in order to bridge the gap between the laboratory-based status and the reality of biomedical applications.

Highly stable triple helix formation by homopyrimidine (l)-acyclic threoninol nucleic acids with single stranded DNA and RNA

2015 ◽  
Vol 13 (8) ◽  
pp. 2366-2374 ◽  
Author(s):  
Vipin Kumar ◽  
Venkitasamy Kesavan ◽  
Kurt V. Gothelf
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Triple Helix ◽  
Helical Structures ◽  
Single Stranded Dna ◽  
Dna And Rna ◽  
Helix Formation ◽  
Triple Helix Formation

Homopyrimidine acyclic (l)-threoninol nucleic acid (aTNA) was synthesized and found to form highly stable (l)-aTNA–DNA–(l)-aTNA and (l)-aTNA–RNA–(l)-aTNA triple helical structures.

scholarly journals Polyamines and Their Role in Virus Infection

2017 ◽  
Vol 81 (4) ◽  
Author(s):  
Bryan C. Mounce ◽  
Michelle E. Olsen ◽  
Marco Vignuzzi ◽  
John H. Connor
Keyword(s):  
Protein Synthesis ◽  
Nucleic Acid ◽  
Mammalian Cells ◽  
Cellular Proliferation ◽  
Polyamine Synthesis ◽  
Host Interactions ◽  
Dna And Rna ◽  
Rna Polymerization ◽  
Nucleic Acid Conformation

SUMMARY Polyamines are small, abundant, aliphatic molecules present in all mammalian cells. Within the context of the cell, they play a myriad of roles, from modulating nucleic acid conformation to promoting cellular proliferation and signaling. In addition, polyamines have emerged as important molecules in virus-host interactions. Many viruses have been shown to require polyamines for one or more aspects of their replication cycle, including DNA and RNA polymerization, nucleic acid packaging, and protein synthesis. Understanding the role of polyamines has become easier with the application of small-molecule inhibitors of polyamine synthesis and the use of interferon-induced regulators of polyamines. Here we review the diverse mechanisms in which viruses require polyamines and investigate blocking polyamine synthesis as a potential broad-spectrum antiviral approach.

scholarly journals Stabilization and ATP-binding for tandem RRM domains of ALS-causing TDP-43 and hnRNPA1

2020 ◽  
Author(s):  
Mei Dang ◽  
Yifan Li ◽  
Jianxing Song
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Conformational Dynamics ◽  
Md Simulations ◽  
Human Diseases ◽  
Atp Binding ◽  
Nucleic Acid Binding ◽  
General Role ◽  
Nmr Characterization

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RRM domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including ALS, FTD, AD and MSP. Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: 1) very unexpectedly, upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. 2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity higher to the tethered than isolated forms. 3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1-RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.

scholarly journals Dissecting and predicting different types of binding sites in nucleic acids based on structural information

2021 ◽  
Author(s):  
Zheng Jiang ◽  
Si-Rui Xiao ◽  
Rong Liu
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Binding Sites ◽  
Structural Information ◽  
Machine Learning Algorithms ◽  
Nucleic Acid Binding ◽  
Integrative Framework ◽  
Dna And Rna ◽  
Feature Spaces ◽  
Critical Binding

Abstract The biological functions of DNA and RNA generally depend on their interactions with other molecules, such as small ligands, proteins and nucleic acids. However, our knowledge of the nucleic acid binding sites for different interaction partners is very limited, and identification of these critical binding regions is not a trivial work. Herein, we performed a comprehensive comparison between binding and nonbinding sites and among different categories of binding sites in these two nucleic acid classes. From the structural perspective, RNA may interact with ligands through forming binding pockets and contact proteins and nucleic acids using protruding surfaces, while DNA may adopt regions closer to the middle of the chain to make contacts with other molecules. Based on structural information, we established a feature-based ensemble learning classifier to identify the binding sites by fully using the interplay among different machine learning algorithms, feature spaces and sample spaces. Meanwhile, we designed a template-based classifier by exploiting structural conservation. The complementarity between the two classifiers motivated us to build an integrative framework for improving prediction performance. Moreover, we utilized a post-processing procedure based on the random walk algorithm to further correct the integrative predictions. Our unified prediction framework yielded promising results for different binding sites and outperformed existing methods.

scholarly journals The Intersection of Purine and Mitochondrial Metabolism in Cancer

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2603
Author(s):  
Humberto De Vitto ◽  
Danushka B. Arachchige ◽  
Brian C. Richardson ◽  
Jarrod B. French
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Cancer Progression ◽  
Critical Role ◽  
Building Blocks ◽  
Mitochondrial Metabolism ◽  
Growth And Survival ◽  
Dna And Rna ◽  
Purines And Pyrimidines

Nucleotides are essential to cell growth and survival, providing cells with building blocks for DNA and RNA, energy carriers, and cofactors. Mitochondria have a critical role in the production of intracellular ATP and participate in the generation of intermediates necessary for biosynthesis of macromolecules such as purines and pyrimidines. In this review, we highlight the role of purine and mitochondrial metabolism in cancer and how their intersection influences cancer progression, especially in ovarian cancer. Additionally, we address the importance of metabolic rewiring in cancer and how the evolving landscape of purine synthesis and mitochondria inhibitors can be potentially exploited for cancer treatment.

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