Stabilization of Telomeric I‐Motif Structures by (2′<i>S</i>)‐2′‐Deoxy‐2′‐<i>C</i>‐Methylcytidine Residues

Aviñó, Anna; Dellafiore, María Andrea; Gargallo, Raimundo; González, Carlos; Iribarren, Adolfo M.; Montserrat, Javier M.; Eritja, Ramón

doi:10.1002/cbic.201700112

Cited by 13 publications

(7 citation statements)

References 48 publications

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“…Following these interesting observations, Aviñó et al. investigated the effect of ( 2 ′ S )-2′-deoxy-2′- C -methyl-cytidine units (C Me Up) (Figure 2B ) on telomeric i-motif structures ( 46 ). This modification adopts mainly a C3′- endo sugar pucker with the methyl group at C2′ in the ‘arabino’ (or β) orientation.…”

Section: Factors Affecting the Stability Of I-motif Structuresmentioning

confidence: 99%

i-Motif DNA: structural features and significance to cell biology

Assi

Garavís

González

et al. 2018

Nucleic Acids Research

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292

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The i-motif represents a paradigmatic example of the wide structural versatility of nucleic acids. In remarkable contrast to duplex DNA, i-motifs are four-stranded DNA structures held together by hemi- protonated and intercalated cytosine base pairs (C:C+). First observed 25 years ago, and considered by many as a mere structural oddity, interest in and discussion on the biological role of i-motifs have grown dramatically in recent years. In this review we focus on structural aspects of i-motif formation, the factors leading to its stabilization and recent studies describing the possible role of i-motifs in fundamental biological processes.

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Section: Factors Affecting the Stability Of I-motif Structuresmentioning

confidence: 99%

i-Motif DNA: structural features and significance to cell biology

Assi

Garavís

González

et al. 2018

Nucleic Acids Research

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304

292

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“…However, for multiple oncogenes such as KRAS and EGFR , efficiency of the detection can be low as a result of severe off‐target binding by the probe to other parts of the human genome . It is argued in multiple reports that to address this issue, the assessment of the hybridisation kinetics and thermodynamics has to be conducted under biologically relevant conditions …”

Section: Introductionmentioning

confidence: 99%

“…To date, hybridisation of DNA and RNA targets by short oligonucleotide probes is assessed by using thermal denaturation experiments, which provide a midpoint of duplex denaturation, called a melting temperature ( T m ). The T m value is used to compare target recognition by different strands and to select the most appropriate probe for, for example, polymerase chain reaction (PCR), sequencing, or amplification of free nucleic acid targeting . However, besides sequence content, the T m value is a function of several other parameters, such as strand concentration, salt concentration, microenvironment, and pH .…”

Section: Introductionmentioning

confidence: 99%

Improving the Design of Synthetic Oligonucleotide Probes by Fluorescence Melting Assay

et al. 2018

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Nucleic acid hybridisation plays a key role in many biological processes, including transcription, translation, and regulation of gene expression. Several sophisticated applications rely on this fundamental interaction, including the polymerase chain reaction, sequencing, and gene therapy. To target a nucleic acid sequence specifically, synthetic oligonucleotides with a suitable affinity and specificity towards the target need to be designed. The affinity of potential probes or therapeutic agents to their target sequence is generally investigated by melting experiments, which break the hydrogen-bonding and stacking interactions that stabilise the double helix resulting in the formation of two single strands. In this paper, we report a comparative study of hybridisation for short fluorescent oligonucleotides labelled with cyanine and ATTO dyes, performed by the currently used UV melting assay and by a more sensitive fluorescence melting experiment. Using different oligonucleotide sequences in the concentration range of 5 nm to 2 μm, we observed a stabilising effect of the fluorophores on the duplexes, especially at low concentrations. We paid particular attention to the effect of polycations and to molecular crowding as major parameters that define the stability and the geometry of nucleic acid duplexes in biological samples. We also demonstrated how the fluorometry-based melting data could aid the design of a probe targeting a human BRAF gene fragment to reduce the off-target binding by a factor of seven.

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“…Also, notable increases in the thermostabilities (6.0−7.5 °C) were observed when the pH 1 H NMR spectra were recorded of selected duplexes (entries 1, 2, and 4, Figure 4) with the aim of observing the distinct N3 imino protons of hemiprotonated C•C + pairs at 15−16 ppm (see Supporting Information, Figure S2). 42,43 However, whereas sharp and well-defined signals were observed for all duplexes, no peaks appeared at 15−16 ppm. In general, all imino protons of the duplexes could not be accounted for in the spectra, but this is likely due to increased exchange rates of the imino protons situated in terminal base pairs or in slightly distorted base pairs adjacent to the C•C mispair.…”

Section: ■ Results and Discussionmentioning

confidence: 90%

Double-Headed 2′-Deoxynucleotides That Hybridize to DNA and RNA Targets via Normal and Reverse Watson–Crick Base Pairs

Beck

Nielsen

2022

J. Org. Chem.

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Through the use of modified nucleotides, synthetic nucleic acids have found several fields of application within biotechnology and in the pharmaceutical industry. We have previously introduced nucleotides with an additional functional nucleobase linked to C2′ of arabinonucleotides (B X ). These double-headed nucleotides fit neatly into DNA·DNA duplexes, where they can replace the corresponding natural dinucleotides and thus condense the molecular information. Here, we introduce a 2′-deoxy version of the B X design with inversion of the C2′ stereochemistry ( d S B X ) with the aim of obtaining improved RNA recognition. Specifically, d S B X analogues with cytosine or isocytosine attached to C2′ of 2′-deoxyuridine ( d S U C and d S U iC ) were synthesized and evaluated in duplexes. Whereas the d S B X design did not outperform the B X design in terms of mimicking dinucleotides in nucleic acid duplexes, it was able to engage in reverse Watson–Crick pairing using its 2′-base. This was evident from the ability of the d S U C cytosine to form stable mis-matching base pairs with opposite cytosines identified as hemiprotonated C·C+ pairs. Furthermore, specific base-pairing with guanine was only observed for the isocytosine-bearing d S U iC monomer. Very stable duplexes were obtained with d S U C/iC monomers in each strand indicating that fully modified double-headed nucleic acid sequences could be based on the d S B X design.

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Stabilization of Telomeric I‐Motif Structures by (2′S)‐2′‐Deoxy‐2′‐C‐Methylcytidine Residues

Cited by 13 publications

References 48 publications

i-Motif DNA: structural features and significance to cell biology

i-Motif DNA: structural features and significance to cell biology

Improving the Design of Synthetic Oligonucleotide Probes by Fluorescence Melting Assay

Double-Headed 2′-Deoxynucleotides That Hybridize to DNA and RNA Targets via Normal and Reverse Watson–Crick Base Pairs

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