Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Backbone-free duplex-stacked monomer nucleic acids exhibiting Watson-Crick selectivity.

ABSTRACT: We demonstrate that nucleic acid (NA) mononucleotide triphosphates (dNTPs and rNTPs), at sufficiently high concentration and low temperature in aqueous solution, can exhibit a phase transition in which chromonic columnar liquid crystal ordering spontaneously appears. Remarkably, this polymer-free state exhibits, in a self-assembly of NA monomers, the key structural elements of biological nucleic acids, including: long-ranged duplex stacking of base pairs, complementarity-dependent partitioning of molecules, and Watson-Crick selectivity, such that, among all solutions of adenosine, cytosine, guanine, and thymine NTPs and their binary mixtures, duplex columnar ordering is most stable in the A-T and C-G combinations.

SUBMITTER: Smith GP

PROVIDER: S-EPMC6099888 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Backbone-free duplex-stacked monomer nucleic acids exhibiting Watson-Crick selectivity.

Smith Gregory P GP Fraccia Tommaso P TP Todisco Marco M Zanchetta Giuliano G Zhu Chenhui C Hayden Emily E Bellini Tommaso T Clark Noel A NA

Proceedings of the National Academy of Sciences of the United States of America 20180702 33

We demonstrate that nucleic acid (NA) mononucleotide triphosphates (dNTPs and rNTPs), at sufficiently high concentration and low temperature in aqueous solution, can exhibit a phase transition in which chromonic columnar liquid crystal ordering spontaneously appears. Remarkably, this polymer-free state exhibits, in a self-assembly of NA monomers, the key structural elements of biological nucleic acids, including: long-ranged duplex stacking of base pairs, complementarity-dependent partitioning o ...[more]

PMID: 29967169

Similar Datasets

Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry.

Project description:We report on the fate of nucleic acids conformation in the gas phase as sampled using native mass spectrometry coupled to ion mobility spectrometry. On the basis of several successful reports for proteins and their complexes, the technique has become popular in structural biology, and the conformation survival becomes more and more taken for granted. Surprisingly, we found that DNA and RNA duplexes, at the electrospray charge states naturally obtained from native solution conditions (?100 mM aqueous NH4OAc), are significantly more compact in the gas phase compared to the canonical solution structures. The compaction is observed for all duplex sizes (gas-phase structures are more compact than canonical B-helices by ?20% for 12-bp, and by up to ?30% for 36-bp duplexes), and for DNA and RNA alike. Molecular modeling (density functional calculations on small helices, semiempirical calculations on up to 12-bp, and molecular dynamics on up to 36-bp duplexes) demonstrates that the compaction is due to phosphate group self-solvation prevailing over Coulomb repulsion. Molecular dynamics simulations starting from solution structures do not reproduce the experimental compaction. To be experimentally relevant, molecular dynamics sampling should reflect the progressive structural rearrangements occurring during desolvation. For nucleic acid duplexes, the compaction observed for low charge states results from novel phosphate-phosphate hydrogen bonds formed across both grooves at the very late stages of electrospray.

| S-EPMC5445532 | biostudies-literature

Loop and backbone modifications of peptide nucleic acid improve g-quadruplex binding selectivity.

Project description:Targeting guanine (G) quadruplex structures is an exciting new strategy with potential for controlling gene expression and designing anticancer agents. Guanine-rich peptide nucleic acid (PNA) oligomers bind to homologous DNA and RNA to form hetero-G-quadruplexes but can also bind to complementary cytosine-rich sequences to form heteroduplexes. In this study, we incorporated backbone modifications into G-rich PNAs to improve the selectivity for quadruplex versus duplex formation. Incorporation of abasic sites as well as chiral modifications to the backbone were found to be effective strategies for improving selectivity as shown by UV-melting and surface plasmon resonance measurements. The enhanced selectivity is due primarily to decreased affinity for complementary sequences, since binding to the homologous DNA to form PNA-DNA heteroquadruplexes retains high affinity. The improved selectivity of these PNAs is an important step toward using PNAs for regulating gene expression by G-quadruplex formation.

| S-EPMC2819988 | biostudies-literature

Dynamical treatment of charge transfer through duplex nucleic acids containing modified adenines.

Project description:We address the issue of whether chemical alterations of nucleobases are an effective tool to modulate charge transfer through DNA molecules. Our investigation uses a multilevel computational approach based on classical molecular dynamics and quantum chemistry. We find yet another piece of evidence that structural fluctuations are a key factor to determine the electronic structure of double-stranded DNA. We argue that the electronic structure and charge transfer ability of flexible polymers is the result of a complex intertwining of various structural, dynamical and chemical factors. Chemical intuition may be used to design molecular wires, but this is not the sole component in the complex charge transfer mechanism through DNA.

| S-EPMC3903158 | biostudies-literature

Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity.

Project description:Multiple lines of evidence support the hypothesis that the early evolution of life was dominated by RNA, which can both transfer information from generation to generation through replication directed by base-pairing, and carry out biochemical activities by folding into functional structures. To understand how life emerged from prebiotic chemistry we must therefore explain the steps that led to the emergence of the RNA world, and in particular, the synthesis of RNA. The generation of pools of highly pure ribonucleotides on the early Earth seems unlikely, but the presence of alternative nucleotides would support the assembly of nucleic acid polymers containing nonheritable backbone heterogeneity. We suggest that homogeneous monomers might not have been necessary if populations of heterogeneous nucleic acid molecules could evolve reproducible function. For such evolution to be possible, function would have to be maintained despite the repeated scrambling of backbone chemistry from generation to generation. We have tested this possibility in a simplified model system, by using a T7 RNA polymerase variant capable of transcribing nucleic acids that contain an approximately 11 mixture of deoxy- and ribonucleotides. We readily isolated nucleotide-binding aptamers by utilizing an in vitro selection process that shuffles the order of deoxy- and ribonucleotides in each round. We describe two such RNA/DNA mosaic nucleic acid aptamers that specifically bind ATP and GTP, respectively. We conclude that nonheritable variations in nucleic acid backbone structure may not have posed an insurmountable barrier to the emergence of functionality in early nucleic acids.

| S-EPMC3158193 | biostudies-literature

Cell-free fetal nucleic acids in amniotic fluid.

Project description:BackgroundResearch into cell-free fetal (cff) nucleic acids has primarily focused on maternal plasma; however, cff DNA and RNA are also detectable in other body fluids such as amniotic fluid (AF). In AF, cff DNA is present in much greater concentrations than in maternal plasma and represents a pure fetal sample uncontaminated by maternal- and trophoblast-derived nucleic acids. The aim of this review was to summarize the current knowledge on cff nucleic acids in AF and to outline future research directions.MethodsMEDLINE and PREMEDLINE were searched up to August 2010 for original investigations of cell-free RNA or DNA in AF. Sixteen studies were included in the review.ResultsAF cff DNA represents a physiologically separate pool from cff DNA in maternal plasma. The placenta is not a major source of nucleic acids in AF. It is feasible to isolate cff nucleic acids from small volumes of discarded AF supernatant in sufficient quality and quantity to perform microarray studies and downstream applications such as pathway analysis. This 'discovery-driven approach' has resulted in new information on the pathogenesis of Down syndrome and polyhydramnios. There is otherwise a paucity of information relating to the basic biology and clinical applications of cff nucleic acids in AF.ConclusionsAF supernatant is a valuable and widely available but under-utilized biological resource. Further studies of cff nucleic acids in AF may lead to new insights into human fetal development and ultimately new approaches to antenatal treatment of human disease.

| S-EPMC3072021 | biostudies-literature

Tunable Duplex Semiquantitative Detection of Nucleic Acids with a Visual Lateral Flow Immunoassay Readout.

Project description:Quantitative nucleic acid amplification testing (NAAT) is a key enabling technology for infectious disease management, especially in instances where viral load informs therapeutic decisions. Inadequate access to quantitative NAATs remains a challenge to the successful deployment of antiretroviral therapy (ART) regimens for patients with chronic hepatitis B virus (CHB) in low resourced settings (LRS). Current field-deployable NAATs are generally qualitative (yes/no) rather than quantitative in nature, making them ill-suited for viral load monitoring programs for CHB patients. Here, we report the development of a proof-of-concept molecular diagnostic test, the semiquantitative ligation and amplification (SQLA) assay, which achieves semiquantitative detection of input target DNA at two independently tunable detection thresholds with a simple visual readout. The SQLA assay utilizes a duplex competitive thermophilic helicase-dependent amplification (tHDA) chemistry and can be performed in under 1 h.

| S-EPMC10017168 | biostudies-literature

Equipment-free, salt-mediated immobilization of nucleic acids for nucleic acid lateral flow assays.

Project description:As the world has been facing several deadly virus crises, including Zika virus disease, Ebola virus disease, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Coronavirus disease 2019 (COVID-19), lateral flow assays (LFAs), which require minimal equipment for point-of-care of viral infectious diseases, are garnering much attention. Accordingly, there is an increasing demand to reduce the time and cost required for manufacturing LFAs. The current study introduces an equipment-free method of salt-mediated immobilization of nucleic acids (SAIoNs) for LFAs. Compared to general DNA immobilization methods such as streptavidin-biotin, UV-irradiation, and heat treatment, our method does not require special equipment (e.g., centrifuge, UV-crosslinker, heating device); therefore, it can be applied in a resource-limited environment with reduced production costs. The immobilization process was streamlined and completed within 30 min. Our method improved the color intensity signal approximately 14 times compared to the method without using SAIoNs and exhibited reproducibility with the long-term storage stability. The proposed method can be used to detect practical targets (e.g., SARS-CoV-2) and facilitates highly sensitive and selective detection of target nucleic acids with multiplexing capability and without any cross-reactivity. This novel immobilization strategy provides a basis for easily and inexpensively developing nucleic acid LFAs combined with various types of nucleic acid amplification.

| S-EPMC9758654 | biostudies-literature

A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids.

Project description:The physicochemical properties of nucleic acids are dominated by their highly charged phosphodiester backbone chemistry. This polyelectrolyte structure decouples information content (base sequence) from bulk properties, such as solubility, and has been proposed as a defining trait of all informational polymers. However, this conjecture has not been tested experimentally. Here, we describe the encoded synthesis of a genetic polymer with an uncharged backbone chemistry: alkyl phosphonate nucleic acids (phNAs) in which the canonical, negatively charged phosphodiester is replaced by an uncharged P-alkyl phosphonodiester backbone. Using synthetic chemistry and polymerase engineering, we describe the enzymatic, DNA-templated synthesis of P-methyl and P-ethyl phNAs, and the directed evolution of specific streptavidin-binding phNA aptamer ligands directly from random-sequence mixed P-methyl/P-ethyl phNA repertoires. Our results establish an example of the DNA-templated enzymatic synthesis and evolution of an uncharged genetic polymer and provide a foundational methodology for their exploration as a source of novel functional molecules.

| S-EPMC6542681 | biostudies-literature

Circulating Cell-Free Nucleic Acids: Main Characteristics and Clinical Application.

Project description:Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of several important biomarkers including cell-free nucleic acids (cf-NAs). Cf-DNA is widely used in prenatal testing in order to characterize fetal genetic disorders. Analysis of cf-DNA may provide information about the mutation profile of tumor cells, while cell-free non-coding RNAs are promising biomarker candidates in the diagnosis and prognosis of cancer. Many of these markers have the potential to help clinicians in therapy selection and in the follow-up of patients. Thus, cf-NA-based diagnostics represent a new path in personalized medicine. Although several reviews are available in the field, most of them focus on a limited number of cf-NA types. In this review, we give an overview about all known cf-NAs including cf-DNA, cf-mtDNA and cell-free non-coding RNA (miRNA, lncRNA, circRNA, piRNA, YRNA, and vtRNA) by discussing their biogenesis, biological function and potential as biomarker candidates in liquid biopsy. We also outline possible future directions in the field.

| S-EPMC7555669 | biostudies-literature

Technical and Methodological Aspects of Cell-Free Nucleic Acids Analyzes.

Project description:Analyzes of cell-free nucleic acids (cfNAs) have shown huge potential in many biomedical applications, gradually entering several fields of research and everyday clinical care. Many biological properties of cfNAs can be informative to gain deeper insights into the function of the organism, such as their different types (DNA, RNAs) and subtypes (gDNA, mtDNA, bacterial DNA, miRNAs, etc.), forms (naked or vesicle bound NAs), fragmentation profiles, sequence composition, epigenetic modifications, and many others. On the other hand, the workflows of their analyzes comprise many important steps, from sample collection, storage and transportation, through extraction and laboratory analysis, up to bioinformatic analyzes and statistical evaluations, where each of these steps has the potential to affect the outcome and informational value of the performed analyzes. There are, however, no universal or standard protocols on how to exactly proceed when analyzing different cfNAs for different applications, at least according to our best knowledge. We decided therefore to prepare an overview of the available literature and products commercialized for cfNAs processing, in an attempt to summarize the benefits and limitations of the currently available approaches, devices, consumables, and protocols, together with various factors influencing the workflow, its processes, and outcomes.

| S-EPMC7697251 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data