Double-headed nucleic acids condense the molecular information of DNA to half the number of nucleotides

Beck, Kasper M.; Sharma, Pawan K.; Hornum, Mick; Risgaard, Nikolaj Alexander; Nielsen, P. H.

doi:10.1039/d1cc03539h

Cited by 4 publications

(11 citation statements)

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“…Also, the discrimination of almost all mismatches is excellent as they range from 8.0-16.0 °C [21][22][23][24] with the only exceptions being the D•C of U D (5.5 °C) [23] and ClU•G of U ClU (3.0 °C). In this context we are convinced that the poor discrimination of T•G mismatches that was also found for our previous A T and G T monomers (1.5-3.0 °C) [24,25] can be improved as well by the replacement of thymine with 5-chlorouracil.…”

Section: Hybridization Studiessupporting

confidence: 70%

“…Recently, we have focused on C2' functionalized double-headed arabinonucleotides with methylene-linkers (U X , Figure 1A), as they can form WatsonÀ Crick base pairs with both nucleobases and thereby act as condensed dinucleotides in a DNA duplex. [20][21][22][23][24][25][26] Encouragingly, molecular dynamics studies have shown that local adjustments of the backbone counteract the structural alteration induced by the incorporation of a double-headed nucleotide, so that the overall B-type duplex of DNA is retained. [23] Moreover, the thermal duplex stability is not particularly affected (� 4.0 °C) [20][21][22][23][24][25] when dinucleotides are replaced with the corresponding double-headed nucleotides.…”

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confidence: 99%

“…[20][21][22][23][24][25][26] Encouragingly, molecular dynamics studies have shown that local adjustments of the backbone counteract the structural alteration induced by the incorporation of a double-headed nucleotide, so that the overall B-type duplex of DNA is retained. [23] Moreover, the thermal duplex stability is not particularly affected (� 4.0 °C) [20][21][22][23][24][25] when dinucleotides are replaced with the corresponding double-headed nucleotides.…”

mentioning

confidence: 99%

“…Considerable stability increases of up to 14 °C have been obtained by placing two double-headed nucleotides in each strand of a duplex, [24] and also, duplexes consisting exclusively of double-headed nucleotides have proved viable with a remarkable 27.0 °C increase for a 5-mer duplex with 10 WatsonÀ Crick base pairs compared to the 10-mer reference duplex. [25] This condensation of molecular information to fewer nucleotides reduces the molecular weight and the number of negative charges for a given nucleotide sequence, which may prove beneficial in future applications.…”

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confidence: 99%

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Double‐Headed Nucleotides with Increased Base‐Pairing Affinity and Specificity

et al. 2021

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Double-headed nucleotides, i. e., nucleotides that hold two nucleobases each, have been shown to be double-functional in DNA duplexes by forming two sets of WatsonÀ Crick base pairs, and thus mimicking dinucleotides. Herein, we present three new double-headed nucleotides, U T + , U A + and U ClU , with the non-natural nucleobases 5-(3-aminopropynyl)uracil (T +), 7-(3aminopropynyl)-7-deazaadenine (A +) and 5-chlorouracil (ClU) attached to the 2'-position of arabinouridine via a methylenelinker. With extended π-systems and amino groups for electro-static interaction with the DNA backbone, incorporation of U T + and U A + increased duplex stability compared to their unmodified predecessors, U T and U A . For U T + , discrimination of mismatches was slightly improved compared to U T , whereas this was not the case for U A + . The U ClU analogue also increased duplex stability compared to U T and provided better mismatch discrimination than both U T and U T + . Thereby it represents the leading bis-uracil double-headed nucleotide analogue.

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Section: Hybridization Studiessupporting

confidence: 70%

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confidence: 99%

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Double‐Headed Nucleotides with Increased Base‐Pairing Affinity and Specificity

et al. 2021

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“…18−20 Multiple incorporations in both strands of the duplex are also tolerated, 19 and even fully modified 5-mers have been shown to form double-headed nucleic acid duplexes with increased stability (+27.0 °C) compared to the 10-mer DNA reference duplex with the same nucleobase sequence. 20 As the monomers display efficient mismatch discrimination on both nucleobases, double-headed nucleotides effectively function as condensed dinucleotides in dsDNA. In contrast, notable reductions in the thermostabilities of 3.5−10.5 °C were observed for DNA•RNA duplexes containing the B X monomers.…”

Section: ■ Introductionmentioning

confidence: 99%

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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A Facile Label‐Free Colorimetric Assay for DNase I Activity Based on the Peroxidase‐Like Activity of Functional Nucleic Acids

Song,

Yan,

Sun

et al. 2024

ChemBioChem

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DNase I plays a crucial role in fundamental biological processes, including gene expression, DNA repair, and apoptosis. Therefore, it is important to develop a simple and efficient method to detect DNase I activity. In this work, a colorimetric assay based on functional nucleic acid for sensitive DNase I detection was reported. The functional nucleic acids with G‐rich bases exhibit peroxidase‐like activity under acetic acid conditions, capable of catalyzing the oxidation of chromogenic substrate 3,3',5,5'‐tetramethylbenzidine (TMB). The specific nucleic acid is designed as the substrate for DNase I, which can hydrolyze the strand and reduce the catalytic activity of the reaction system. Based on this, a sensitive, simple, efficient, and cost‐effective colorimetric detection platform was constructed for the quantitative analysis of DNase I. The detection limit (3σ/s) for DNase I was 0.046 U/mL with a linear range of 0.1–1 U/mL. Moreover, the practicality of this colorimetric detection platform was demonstrated by detecting DNase I in human serum.

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Double-headed nucleic acids condense the molecular information of DNA to half the number of nucleotides

Abstract: Nucleotide monomers that hold two nucleobases each, i.e. double-headed nucleotides, have been shown to form two sets of functional Watson–Crick base pairs when incorporated into dsDNA, and they hereby behave...

Cited by 4 publications

References 16 publications

Double‐Headed Nucleotides with Increased Base‐Pairing Affinity and Specificity

Double‐Headed Nucleotides with Increased Base‐Pairing Affinity and Specificity

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

A Facile Label‐Free Colorimetric Assay for DNase I Activity Based on the Peroxidase‐Like Activity of Functional Nucleic Acids

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