Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Influence of 5-N-carboxamide modifications on the thermodynamic stability of oligonucleotides.

ABSTRACT: We have recently shown that the incorporation of modified nucleotides such as 5-N-carboxamide-deoxyuridines into random nucleic acid libraries improves success rates in SELEX experiments and facilitates the identification of ligands with slow off-rates. Here we report the impact of these modifications on the thermodynamic stability of both duplexes and intramolecular 'single-stranded' structures. Within duplexes, large, hydrophobic naphthyl groups were destabilizing relative to the all natural DNA duplex, while the hydrophilic groups exhibited somewhat improved duplex stability. All of the significant changes in stability were driven by opposing contributions from the enthalpic and entropic terms. In contrast, both benzyl and naphthyl modifications stabilized intramolecular single-stranded structures relative to their natural DNA analogs, consistent with the notion that intramolecular folding allows formation of novel, stabilizing hydrophobic interactions. Imino proton NMR data provided evidence that elements of the folded structure form at temperatures well below the Tm, with a melting transition that is distinctly less cooperative when compared to duplex DNA. Although there are no data to suggest that the unmodified DNA sequences fold into structures similar to their modified analogs, this still represents clear evidence that these modifications impart thermodynamic stability to the folded structure not achievable with unmodified DNA.

SUBMITTER: Wolk SK

PROVIDER: S-EPMC4627095 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Non-Nucleosidic Analogues of Polyaminonucleosides and Their Influence on Thermodynamic Properties of Derived Oligonucleotides.

Project description:The rationale for the synthesis of cationic modified nucleosides is higher expected nuclease resistance and potentially better cellular uptake due to an overall reduced negative charge based on internal charge compensation. Due to the ideal distance between cationic groups, polyamines are perfect counterions for oligodeoxyribonucleotides. We have synthesized non-nucleosidic analogues built from units that carry different diol structures instead of sugar residues and functionalized with polyamines. The non-nucleosidic analogues were attached as internal or 5'-terminal modifications in oligodeoxyribonucleotide strands. The thermodynamic studies of these polyaminooligonucleotide analogues revealed stabilizing or destabilizing effects that depend on the linker or polyamine used.

| S-EPMC6332422 | biostudies-literature

A statistical thermodynamic model for investigating the stability of DNA sequences from oligonucleotides to genomes.

Project description:We describe the development and testing of a simple statistical mechanics methodology for duplex DNA applicable to sequences of any composition and extensible to genomes. The microstates of a DNA sequence are modeled in terms of blocks of basepairs that are assumed to be fully closed (paired) or open. This approach generates an ensemble of bubblelike microstates that are used to calculate the corresponding partition function. The energies of the microstates are calculated as additive contributions from hydrogen bonding, basepair stacking, and solvation terms parameterized from a comprehensive series of molecular dynamics simulations including solvent and ions. Thermodynamic properties and nucleotide stability constants for DNA sequences follow directly from the partition function. The methodology was tested by comparing computed free energies per basepair with the experimental melting temperatures of 60 oligonucleotides, yielding a correlation coefficient of -0.96. The thermodynamic stability of genic/nongenic regions was tested in terms of nucleotide stability constants versus sequence for the Escherichia coli K-12 genome. It showed clear differentiation of the genes from promoters and captures genic regions with a sensitivity of 0.94. The statistical thermodynamic model presented here provides a seemingly new handle on the challenging problem of interpreting genomic sequences.

| S-EPMC4052264 | biostudies-literature

The effect of chemical modifications on the thermal stability of different G-quadruplex-forming oligonucleotides.

Project description:A systematic study of the thermal and conformational properties of chemically modified G-quadruplexes of different molecularities is reported. The effect of backbone charge and atom size, thymine/uracyl substitution as well as the effect of modification at the ribose 2'-position was analyzed by UV spectroscopy. Additional calorimetric studies were performed on different modified forms of the human telomeric sequence. Determination of the differential spectra allowed more insights into the conformational properties of the oligonucleotides. Lack of negative charge at the phosphate backbone yielded to a general destabilization of the G-quadruplex structure. On the other hand, substitution of thymine with uracyl resulted in a moderate or strong stabilization of the structure. Additional modification at the sugar 2'-position gave rise to different effects depending on the molecularity of the quadruplex. In particular, loss of hydrogen bond capacity at the 2'-position strongly affected the conformation of the G-quadruplex. Altogether, these results demonstrate that the effect of some modifications depends on the sequence context, thus providing helpful information for the use of chemically modified quadruplexes as therapeutic agents or as structural elements of supramolecular complexes.

| S-EPMC549566 | biostudies-literature

Interplay of structure, hydration and thermal stability in formacetal modified oligonucleotides: RNA may tolerate nonionic modifications better than DNA.

Project description:DNA and RNA oligonucleotides having formacetal internucleoside linkages between uridine and adenosine nucleosides have been prepared and studied using UV thermal melting, osmotic stress, and X-ray crystallography. Formacetal modifications have remarkably different effects on double helical RNA and DNA-the formacetal stabilizes the RNA helix by +0.7 degrees C but destabilizes the DNA helix by -1.6 degrees C per modification. The apparently hydrophobic formacetal has little effect on hydration of RNA but decreases the hydration of DNA, which suggests that at least part of the difference in thermal stability may be related to differences in hydration. A crystal structure of modified DNA shows that two isolated formacetal linkages fit almost perfectly in an A-type helix (decamer). Taken together, the data suggest that RNA may tolerate nonionic backbone modifications better than DNA. Overall, formacetal appears to be an excellent mimic of phosphate linkage in RNA and an interesting modification for potential applications in fundamental studies and RNA-based gene control strategies, such as RNA interference.

| S-EPMC2823299 | biostudies-literature

Influence of Bacterial Physiology on Processing of Selenite, Biogenesis of Nanomaterials and Their Thermodynamic Stability.

Project description:We explored how Ochrobactrum sp. MPV1 can convert up to 2.5 mM selenite within 120 h, surviving the challenge posed by high oxyanion concentrations. The data show that thiol-based biotic chemical reaction(s) occur upon bacterial exposure to low selenite concentrations, whereas enzymatic systems account for oxyanion removal when 2 mM oxyanion is exceeded. The selenite bioprocessing produces selenium nanomaterials, whose size and morphology depend on the bacterial physiology. Selenium nanoparticles were always produced by MPV1 cells, featuring an average diameter ranging between 90 and 140 nm, which we conclude constitutes the thermodynamic stability range for these nanostructures. Alternatively, selenium nanorods were observed for bacterial cells exposed to high selenite concentration or under controlled metabolism. Biogenic nanomaterials were enclosed by an organic material in part composed of amphiphilic biomolecules, which could form nanosized structures independently. Bacterial physiology influences the surface charge characterizing the organic material, suggesting its diverse biomolecular composition and its involvement in the tuning of the nanomaterial morphology. Finally, the organic material is in thermodynamic equilibrium with nanomaterials and responsible for their electrosteric stabilization, as changes in the temperature slightly influence the stability of biogenic compared to chemogenic nanomaterials.

| S-EPMC6681009 | biostudies-literature

Prediction of antisense oligonucleotides using structural and thermodynamic motifs.

Project description:Specific gene expression regulation strategy using antisense oligonucleotides occupy significant space in recent clinical trials. The therapeutical potential of oligos lies in the identification and prediction of accurate oligonucleotides against specific target mRNA. In this work we present a computational method that is built on Artificial Neural Network (ANN) which could recognize and predict oligonucleotides effectively. In this study first we identified 11 major parameters associated with oligo:mRNA duplex linkage. A feed forward multilayer perceptron ANN classifier is trained with a set of experimentally proven feature vectors. The classifier gives an exact prediction of the input sequences under 2 classes - oligo or non-oligo. On validation, our tool showed comparatively significant accuracy of 92.48% with 91.7% sensitivity and 92.09% specificity. This study was also able to reveal the relative impact of individual parameters we considered on antisense oligonucleotide predictions.

| S-EPMC3530885 | biostudies-other

Thermodynamic Stability of Fenclorim and Clopyralid.

Project description:The present work reports an experimental thermodynamic study of two nitrogen heterocyclic organic compounds, fenclorim and clopyralid, that have been used as herbicides. The sublimation vapor pressures of fenclorim (4,6-dichloro-2-phenylpyrimidine) and of clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) were measured, at different temperatures, using a Knudsen mass-loss effusion technique. The vapor pressures of both crystalline and liquid (including supercooled liquid) phases of fenclorim were also determined using a static method based on capacitance diaphragm manometers. The experimental results enabled accurate determination of the standard molar enthalpies, entropies and Gibbs energies of sublimation for both compounds and of vaporization for fenclorim, allowing a phase diagram representation of the (p,T) results, in the neighborhood of the triple point of this compound. The temperatures and molar enthalpies of fusion of the two compounds studied were determined using differential scanning calorimetry. The standard isobaric molar heat capacities of the two crystalline compounds were determined at 298.15 K, using drop calorimetry. The gas phase thermodynamic properties of the two compounds were estimated through ab initio calculations, at the G3(MP2)//B3LYP level, and their thermodynamic stability was evaluated in the gaseous and crystalline phases, considering the calculated values of the standard Gibbs energies of formation, at 298.15 K. All these data, together with other physical and chemical properties, will be useful to predict the mobility and environmental distribution of these two compounds.

| S-EPMC8746602 | biostudies-literature

Theoretical analysis on thermodynamic stability of chignolin.

Project description:Understanding the dominant factor in thermodynamic stability of proteins remains an open challenge. Kauzmann's hydrophobic interaction hypothesis, which considers hydrophobic interactions between nonpolar groups as the dominant factor, has been widely accepted for about sixty years and attracted many scientists. The hypothesis, however, has not been verified or disproved because it is difficult, both theoretically and experimentally, to quantify the solvent effects on the free energy change in protein folding. Here, we developed a computational method for extracting the dominant factor behind thermodynamic stability of proteins and applied it to a small, designed protein, chignolin. The resulting free energy profile quantitatively agreed with the molecular dynamics simulations. Decomposition of the free energy profile indicated that intramolecular interactions predominantly stabilized collapsed conformations, whereas solvent-induced interactions, including hydrophobic ones, destabilized them. These results obtained for chignolin were consistent with the site-directed mutagenesis and calorimetry experiments for globular proteins with hydrophobic interior cores.

| S-EPMC6435801 | biostudies-literature

Thermodynamic stability of ligand-protected metal nanoclusters.

Project description:Despite the great advances in synthesis and structural determination of atomically precise, thiolate-protected metal nanoclusters, our understanding of the driving forces for their colloidal stabilization is very limited. Currently there is a lack of models able to describe the thermodynamic stability of these 'magic-number' colloidal nanoclusters as a function of their atomic-level structural characteristics. Herein, we introduce the thermodynamic stability theory, derived from first principles, which is able to address stability of thiolate-protected metal nanoclusters as a function of the number of metal core atoms and thiolates on the nanocluster shell. Surprisingly, we reveal a fine energy balance between the core cohesive energy and the shell-to-core binding energy that appears to drive nanocluster stabilization. Our theory applies to both charged and neutral systems and captures a large number of experimental observations. Importantly, it opens new avenues for accelerating the discovery of stable, atomically precise, colloidal metal nanoclusters.

| S-EPMC5504301 | biostudies-literature

The Metabolome Weakens RNA Thermodynamic Stability and Strengthens RNA Chemical Stability.

Project description:We examined the complex network of interactions among RNA, the metabolome, and divalent Mg2+ under conditions that mimic the Escherichia coli cytoplasm. We determined Mg2+ binding constants for the top 15 E. coli metabolites, comprising 80% of the metabolome by concentration at physiological pH and monovalent ion concentrations. These data were used to inform the development of an artificial cytoplasm that mimics in vivo E. coli conditions, which we term "Eco80". We empirically determined that the mixture of E. coli metabolites in Eco80 approximated single-site binding behavior toward Mg2+ in the biologically relevant free Mg2+ range of ∼0.5 to 3 mM Mg2+, using a Mg2+-sensitive fluorescent dye. Effects of Eco80 conditions on the thermodynamic stability, chemical stability, structure, and catalysis of RNA were examined. We found that Eco80 conditions lead to opposing effects on the thermodynamic and chemical stabilities of RNA. In particular, the thermodynamic stability of RNA helices was weakened by 0.69 ± 0.12 kcal/mol, while the chemical stability was enhanced ∼2-fold, which can be understood using the speciation of Mg2+ between weak and strong Mg2+-metabolite complexes in Eco80. Overall, the use of Eco80 reflects RNA function in vivo and enhances the biological relevance of mechanistic studies of RNA.

| S-EPMC9669196 | 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