Double-headed nucleotides as xeno nucleic acids: information storage and polymerase recognition

Beck, Kasper M.; Krogh, Marie B.; Hornum, Mick; Ludford, Paul T.; Tor, Yitzhak; Nielsen, P. H.

doi:10.1039/d0ob01426e

Cited by 12 publications

(27 citation statements)

References 27 publications

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“…One of the UBP

with the strongest N–H⋯N bonds, the GG base pair with a BSO n value of 0.426 has been discussed in so-called mismatched DNA causing genetic diseases [ 137 , 138 ]. The GG base pair has also the capability to form a H-bonding pattern close to that found in NBP

, i.e., being stabilized by three HBs, N–H⋯N, N–H⋯O and C–H⋯O (see Figure 2 ) making this pair an interesting candidate for xenobiology [ 33 , 34 , 139 ].…”

Section: Results and Discussionmentioning

confidence: 99%

“…Recently, modifications of DNA containing four NBP

and four additional UBP

which efficiently replicated [ 32 , 32 ] were reported. A range of UBP

, termed xeno nucleic acids ( XNA

) were introduced [ 33 , 34 ]. XNA

are constructed by replacing natural bases, sugars, and phosphate linkages of DNA with artificial structures in order to synthesize potential alternative genetic materials, which may open new horizons of genetically modified organisms [ 18 , 35 , 36 , 37 , 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

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Hydrogen Bonding in Natural and Unnatural Base Pairs—A Local Vibrational Mode Study

2021

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In this work hydrogen bonding in a diverse set of 36 unnatural and the three natural Watson Crick base pairs adenine (A)–thymine (T), adenine (A)–uracil (U) and guanine (G)–cytosine (C) was assessed utilizing local vibrational force constants derived from the local mode analysis, originally introduced by Konkoli and Cremer as a unique bond strength measure based on vibrational spectroscopy. The local mode analysis was complemented by the topological analysis of the electronic density and the natural bond orbital analysis. The most interesting findings of our study are that (i) hydrogen bonding in Watson Crick base pairs is not exceptionally strong and (ii) the N–H⋯N is the most favorable hydrogen bond in both unnatural and natural base pairs while O–H⋯N/O bonds are the less favorable in unnatural base pairs and not found at all in natural base pairs. In addition, the important role of non-classical C–H⋯N/O bonds for the stabilization of base pairs was revealed, especially the role of C–H⋯O bonds in Watson Crick base pairs. Hydrogen bonding in Watson Crick base pairs modeled in the DNA via a QM/MM approach showed that the DNA environment increases the strength of the central N–H⋯N bond and the C–H⋯O bonds, and at the same time decreases the strength of the N–H⋯O bond. However, the general trends observed in the gas phase calculations remain unchanged. The new methodology presented and tested in this work provides the bioengineering community with an efficient design tool to assess and predict the type and strength of hydrogen bonding in artificial base pairs.

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“…One of the UBP

, i.e., being stabilized by three HBs, N–H⋯N, N–H⋯O and C–H⋯O (see Figure 2 ) making this pair an interesting candidate for xenobiology [ 33 , 34 , 139 ].…”

Section: Results and Discussionmentioning

confidence: 99%

“…Recently, modifications of DNA containing four NBP

and four additional UBP

which efficiently replicated [ 32 , 32 ] were reported. A range of UBP

, termed xeno nucleic acids ( XNA

) were introduced [ 33 , 34 ]. XNA

Section: Introductionmentioning

confidence: 99%

Hydrogen Bonding in Natural and Unnatural Base Pairs—A Local Vibrational Mode Study

2021

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“…Currently, the full set of uridine-based analogues (U C , U G , U T , U A ) have been presented and evaluated together with selected cytosine-and adenosine-based analogues in the form of C C and A T . [23][24][25][26][27] These double-headed nucleotides are wellaccommodated in DNA duplexes when incorporated in exchange for the corresponding dinucleotide ( Figure 1). For instance, when central 5'-UC or 5'-UG dinucleotides are replaced with the U C or U G double-headed nucleotide monomers, respectively, the thermal duplex stability remains intact ( Figure 1, green bars).…”

Section: Introductionmentioning

confidence: 97%

“…The 2′‐bases of U C and U G also display a good mismatch discrimination comparable to that of mismatches involving natural nucleotides (Figure 1, white bars). When U T and U A monomers are incorporated, the duplex is slightly destabilized by 2.5 °C to 3.5 °C [25,27] . While the 2′⋅1′ mismatch discrimination capacity of U T and U A against T, A or C also resemble those of the unmodified duplexes, the discrimination against G is insufficient (1.0–1.5 °C).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, the full set of uridine‐based analogues ( U C , U G , U T , U A ) have been presented and evaluated together with selected cytosine‐ and adenosine‐based analogues in the form of C C and A T [23–27] . These double‐headed nucleotides are well‐accommodated in DNA duplexes when incorporated in exchange for the corresponding dinucleotide (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Double‐Headed Nucleotides with Non‐Native Nucleobases: Synthesis and Duplex Studies

et al. 2021

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Double-headed nucleotides are DNA building blocks that store, in principle, twice as much information as native nucleotides due to the incorporation of an additional functional nucleobase. Herein, we present the development of two new doubleheaded nucleotides, U W and U Z, featuring a methylene-linked 5aza-7-deazaxanthine (Z) and a propynyl-linked pseudouracil (W), respectively, attached to the 2'-position of arabinouridine. These analogs are evaluated in DNA duplexes for their ability to act as dinucleotides, and the base-pairing specificities of the 2'nucleobases are compared to previous analogues. Although an improved discrimination was observed in the context of a cytosine mismatch using U Z , neither of the two new analogs gave rise to increased overall base-pairing fidelity possibly due to the formation of stable wobble pairs. Furthermore, we present an improved synthetic strategy for the preparation of the corresponding diaminopurine analog (U D), in which the key fluoro-to-amino substitution is achieved post-synthetically to avoid the use of doubly protected diaminopurines and complicated deprotections.

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Materialistic Interfaces with Nucleic Acids: Principles and Their Impact

Zhang

et al. 2022

Adv Funct Materials

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Mendelian genetics spark the century‐old revolution in genetic engineering. DNA structural engineering may well spark a similar revolution in chemistry. The first few man‐made DNA structures are purely DNA but increased interest in hybrid DNA with other molecules is regaining popularity. Nucleic acids can interact with non‐nucleic acid‐based materials, showing their materialistic flexibility and potential and the prospect of forming new future materials. This review provides a deep materialistic background based on the interaction of nucleic acids with these non‐nucleic acid‐based materials covering comprehensive topics. The non‐nucleic acid materials are broadly divided into biological materials, for example, small‐biomolecules, peptides, proteins, and lipids, and non‐biological materials consisting of metal ions, chemical molecules, low‐dimensional nanomaterials, and micro‐scale polymers. Of significance, combining the unique properties of nucleic acids with these non‐genetic materials can bring about surprising synergistic characteristics and drive attractive applications in bio‐imaging, chem/bio‐sensing, disease therapies, antimicrobial works, and even information storage.

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Double-headed nucleotides as xeno nucleic acids: information storage and polymerase recognition

Abstract: Xeno nucleic acids (XNAs) are artificial genetic systems based on sugar-modified nucleotides. Herein, we investigate double-headed nucleotides as a new XNA. A new monomer, AT, is presented, and together with...

Cited by 12 publications

References 27 publications

Hydrogen Bonding in Natural and Unnatural Base Pairs—A Local Vibrational Mode Study

Hydrogen Bonding in Natural and Unnatural Base Pairs—A Local Vibrational Mode Study

Double‐Headed Nucleotides with Non‐Native Nucleobases: Synthesis and Duplex Studies

Materialistic Interfaces with Nucleic Acids: Principles and Their Impact

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