Why Does TNA Cross‐Pair More Strongly with RNA Than with DNA? An Answer From X‐ray Analysis

Pallan, Pradeep S.; Wilds, Christopher J.; Wawrzak, Z.; Krishnamurthy, Ramanarayanan; Eschenmoser, Albert; Egli, Martin

doi:10.1002/anie.200352553

Cited by 69 publications

(79 citation statements)

References 22 publications

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“…In the X-ray structures of a B-DNA and an A-DNA duplex, both containing one TNA residue per strand, Egli and co-workers observed a 4′-exo conformation for the TNA residues in both cases. 24,25 Structurally, the all-TNA duplex 1 studied here clearly resembles the A-type helix of RNA as judged from the average values for Figure 6b). Data included: R and of residues 3-7, ε and of residues 2-6, of residues 2-7, and pseudorotation phase angle P of the furanose ring (terminal residues are excluded from the picture).…”

Section: Discussionmentioning

confidence: 88%

The Structure of a TNA−TNA Complex in Solution: NMR Study of the Octamer Duplex Derived from α-(l)-Threofuranosyl-(3′-2′)-CGAATTCG

et al. 2008

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TNA (alpha-( l)-threofuranosyl-(3'-2') nucleic acid) is a nucleic acid in which the ribofuranose building block of the natural nucleic acid RNA is replaced by the tetrofuranose alpha-( l)-threose. This shortens the repetitive unit of the backbone by one bond as compared to the natural systems. Among the alternative nucleic acid structures studied so far in our laboratories in the etiological context, TNA is the only one that exhibits Watson-Crick pairing not only with itself but also with DNA and, even more strongly, with RNA. Using NMR spectroscopy, we have determined the structure of a duplex consisting entirely of TNA nucleotides. The TNA octamer (3'-2')-CGAATTCG forms a right-handed double helix with antiparallel strands paired according to the Watson-Crick mode. The dominant conformation of the sugar units has the 2'- and 3'-phosphodiester substituents in quasi-diaxial position and corresponds to a 4'-exo puckering. With 5.85 A, the average sequential P i -P i+1 distances of TNA are shorter than for A-type DNA (6.2 A). The helix parameters, in particular the slide and x-displacement, as well as the shallow and wide minor groove, place the TNA duplex in the structural vicinity of A-type DNA and RNA.

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Section: Discussionmentioning

confidence: 88%

The Structure of a TNA−TNA Complex in Solution: NMR Study of the Octamer Duplex Derived from α-(l)-Threofuranosyl-(3′-2′)-CGAATTCG

et al. 2008

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“…[4] Crystallographic analysis of B- and A-form duplexes with a single TNA nucleotide inserted into an otherwise natural DNA strand yielded only minor effects on the duplex geometries, base-pair stacking interactions, and the sugar puckers of neighboring native nucleotides. [5] , [6] In both structures, the threose sugar adopts a C4′- exo -pucker with a trans -diaxial orientation of the 3′- and 2′-substituents. The preference for this sugar conformation, irrespective of the A- or B-form geometry, suggests that TNA has a limited range of sugar conformations that are compatible with Watson-Crick base pairing.…”

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confidence: 99%

Structural Insights into Conformation Differences between DNA/TNA and RNA/TNA Chimeric Duplexes

et al. 2016

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Threose nucleic acid (TNA) is an artificial genetic polymer capable of heredity and evolution that is studied in the context of RNA chemical etiology. Its simplified four-carbon threose backbone replaces the five-carbon ribose in natural nucleic acids. Nonetheless, TNA forms stable antiparallel Watson-Crick homoduplexes and heteroduplexes with complimentary DNA and RNA. TNA base pairs with RNA more favorably than DNA, but the reason is unknown. Here, we employ NMR, ITC, UV and CD studies to probe the structural and dynamic properties of RNA/TNA and DNA/TNA heteroduplexes that give rise to the differential stability. The results indicate that TNA templates the structure of heteroduplexes, forcing an A-like helical geometry. Further NMR measurements of kinetic and thermodynamic parameters for individual base pair opening events reveal unexpected asymmetric breathing fluctuations of the DNA/TNA helix, which are also manifested at the molecular level. These results suggest that DNA is unable to fully adapt to the conformational constraints of the rigid TNA backbone and that nucleic acid breathing dynamics are determined from both backbone and base contributions.

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“…Since the conformation of the furanose ring was not restrained during structure calculation, we consider this possibility as unlikely, because restraints imposed by NOEs and coupling constants resulting from a structurally diverse ensemble can usually not be satisfied by one average structure. Another line of experimental evidence supporting a pure 4'-exo conformation in solution are the structures of a dodecamer B-DNA [62] and decamer A-DNA [63] duplex incorporating one TNA residue in each strand (TNA T and TNA A, resp.). Both were determined by X-ray diffraction in the laboratory of Egli.…”

Section: (2'-3')-a-l-threofuranosyl Nucleicmentioning

confidence: 98%

Oligonucleotides with Sugars Other Than Ribo‐ and 2′‐Deoxyribofuranose in the Backbone: the Solution Structures Determined by NMR in the Context of the ‘Etiology of Nucleic Acids’ Project of Albert Eschenmoser

Ebert

Jaun

2010

Chemistry & Biodiversity

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1. Introduction. -Etiology of Nucleic Acids. In the words of Albert Eschenmoser, initiator and spiritus rector of this research project carried out at ETH Zürich and at The Scripps Research Institute (USA) over the last two decades, the goal was to explore the potential of organic chemistry to arrive at an understanding of how and why Nature came to choose the specific structure type of the nucleic acids we know today as the molecular basis of genetic function. The specific property to be compared in this work is a given nucleic acid alternatives capacity for informational Watson -Crick nucleobase pairing, the overall criterion for the selection for study of a given system being a structures potential for constitutional self-assembly as compared to that envisaged for the structure of the natural system itself [1]. Initially, and for the majority of actually synthesized and investigated structures, this latter selection criterion was restricted further by concentrating on alternative nucleic acids in which only the sugar units were varied within the basic architecture of the natural nucleic acids, namely a backbone of (cyclic) sugar units linked by phosphodiester bonds and carrying the canonical nucleobases at C(1') of the sugar (Fig. 1). Therefore, the experimental exploration concentrated on nucleic acids with alternative sugar units that were considered as potentially natural in the sense that they should be derivable from an alternative aldose by the same type of chemistry that allows us to derive the structure of RNA from ribose [1]. This self-restraint to chemically and structurally close relatives of RNA narrowed down the structural space to be explored dramatically and allowed avoiding the speculative question of how an alternative informational biopolymer consisting of building blocks that are structurally much more distant from those of RNA might have self-assembled.Since the aim was to select building blocks that would allow formation of informational pairing systems based on Watson -Crick base pairs, linear or helical translational symmetry of the backbone units along each single strand was required for the conformation in the duplex (pairing conformation). The strategy for finding alternate pairing systems was, therefore, identification of sugar-phosphodiester partial structures that would prefer backbone conformations satisfying this symmetry requirement already in the single strand. Such a preorganization of the single strand in the pairing conformation not only leads to a relatively strain-free duplex (lowering the

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Why Does TNA Cross‐Pair More Strongly with RNA Than with DNA? An Answer From X‐ray Analysis

Cited by 69 publications

References 22 publications

The Structure of a TNA−TNA Complex in Solution: NMR Study of the Octamer Duplex Derived from α-(l)-Threofuranosyl-(3′-2′)-CGAATTCG

The Structure of a TNA−TNA Complex in Solution: NMR Study of the Octamer Duplex Derived from α-(l)-Threofuranosyl-(3′-2′)-CGAATTCG

Structural Insights into Conformation Differences between DNA/TNA and RNA/TNA Chimeric Duplexes

Oligonucleotides with Sugars Other Than Ribo‐ and 2′‐Deoxyribofuranose in the Backbone: the Solution Structures Determined by NMR in the Context of the ‘Etiology of Nucleic Acids’ Project of Albert Eschenmoser

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