<scp>l</scp>-α-Lyxopyranosyl (4‘→3‘) Oligonucleotides:  A Base-Pairing System Containing a Shortened Backbone<sup>1</sup>

Reck, Folkert; Wippo, Harald; Kudick, René; Bolli, Martin H.; Ceulemans, Griet; Krishnamurthy, Ramanarayanan; Eschenmoser, Albert

doi:10.1021/ol990184q

Cited by 26 publications

(30 citation statements)

References 12 publications

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“…11b) also are not able to cross-bind to DNA. 5,112 On the contrary, the a-L-lyxopyranosyl (4 0 ?3 0 ) derivative (Fig. 11c) is able to bind both DNA and RNA, because of the trans-axial arrangement of the phosphodiester groups.…”

Section: Ribose Substitutesmentioning

confidence: 99%

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

et al. 2007

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The understanding of the interaction of chiral species with DNA or RNA is very important for the development of new tools in biology and of new drugs. Several cases in which chirality is a crucial point in determining the DNA binding mode are reviewed and discussed, with the aim of illustrating how chirality can be considered as a tool for improving the understanding of mechanisms and the effectiveness of nucleic acid recognition. The review is divided into two parts: the former describes examples of chiral species interacting with DNA: intercalators, metal complexes, and groove binders; the latter part is dedicated to chirality in DNA analogs, with discussion of phosphate stereochemistry and chirality of ribose substitutes, in particular of peptide nucleic acids (PNAs) for which a number of works have been published recently dealing with the effect of chirality in DNA recognition. The discussion is intended to show how enantiomeric recognition originates at the molecular level, by exploiting the enormous progresses recently achieved in the field of structural characterization of complexes formed by nucleic acid with their ligands by crystallographic and spectroscopic methods. Examples of application of the DNA binding molecules described and the role of chirality in DNA recognition relevant for biotechnology or medicinal chemistry are reported.

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Section: Ribose Substitutesmentioning

confidence: 99%

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

et al. 2007

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“…Indeed, neither the complementary octamer strands (3'-4')prA 8 and (3'-4')prT 8 containing only (3'-4')-phophosdiester links (five bonds per repeating unit) nor the selfcomplementary sequences (3'-4')prA 4 T 4 or (3'-4')prT 4 A 4 did undergo duplex formation [35] [37]. After the synthesis of (2'-4')-a-l-lyxopyranosyl oligonucleotides [29] [31] as the first pairing system with the 4'-phosphate group in axial position, it turned out, however, that pLyxoNA with a (3'-4')-connection of the backbone does form duplexes [35] [37].…”

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

confidence: 99%

“…After the synthesis of (2'-4')-a-l-lyxopyranosyl oligonucleotides [29] [31] as the first pairing system with the 4'-phosphate group in axial position, it turned out, however, that pLyxoNA with a (3'-4')-connection of the backbone does form duplexes [35] [37]. In this pyranosyl nucleic acid, the sugar ring adopts a conformation with the vicinal phosphate groups in axial positions, which maximizes their distance (Fig.…”

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

confidence: 99%

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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“…The experimental strategy is to conceive potentially natural alternatives to the nucleic acid structure, to synthesize such alternatives by chemical methods, and to compare them with the natural nucleic acids with respect to those chemical properties that are fundamental to the biological function of RNA and DNA ( Fig. 1).In the course of these studies it was found that all four members of the family of pentopyranosyl-(4'AE2')-oligonucleotide systems that contain b-ribo, b-xylo-, a-lyxo-or a-arabinopyranosyl units as repeating sugar building blocks are found to be much stronger Watson-Crick base-pairing systems than RNA [1][2][3]. The a-arabinopyranosyl system is the strongest of all, in fact, it belongs to the strongest oligonucleotide base-pairing systems known.…”

mentioning

confidence: 99%

“…In the course of these studies it was found that all four members of the family of pentopyranosyl-(4'AE2')-oligonucleotide systems that contain b-ribo, b-xylo-, a-lyxo-or a-arabinopyranosyl units as repeating sugar building blocks are found to be much stronger Watson-Crick base-pairing systems than RNA [1][2][3]. The a-arabinopyranosyl system is the strongest of all, in fact, it belongs to the strongest oligonucleotide base-pairing systems known.…”

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confidence: 99%

Chemical etiology of nucleic acid structure

Eschenmoser¹,

Krishnamurthy²

2000

Pure and Applied Chemistry

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The synthesis of potentially natural nucleic acid alternatives and comparison of some of their chemical properties with those of RNA and DNA have led to findings that we consider to be relevant in the context of a chemical etiology of nucleic acid structure.Chemical etiology of nucleic acid structure refers to systematic experimental studies aimed at narrowing the diversity of possible answers to the question of why nature chose the structure type of ribofuranosyl nucleic acids, rather than some other family of molecular structures, as the molecular basis of life's genetic system. The experimental strategy is to conceive potentially natural alternatives to the nucleic acid structure, to synthesize such alternatives by chemical methods, and to compare them with the natural nucleic acids with respect to those chemical properties that are fundamental to the biological function of RNA and DNA ( Fig. 1).In the course of these studies it was found that all four members of the family of pentopyranosyl-(4'AE2')-oligonucleotide systems that contain b-ribo, b-xylo-, a-lyxo-or a-arabinopyranosyl units as repeating sugar building blocks are found to be much stronger Watson-Crick base-pairing systems than RNA [1][2][3]. The a-arabinopyranosyl system is the strongest of all, in fact, it belongs to the strongest oligonucleotide base-pairing systems known. We conclude that, whatever the chemical determinants by which nature selected RNA as a genetic system, maximization of base-pairing strengths within the domain of pentose-derived oligonucleotide systems was not the critical selection criterion [4] (Fig. 2).The so far experimentally most comprehensively studied system among the potentially natural sugar-based nucleic acid alternatives is the pyranosyl isomer of RNA. One of the chemical properties of this system provides a transparent illustration of the intrinsic potential of an informational oligomer system to break molecular mirror symmetry. Hemi-self-complementary p-RNA tetramer-2',3'-cyclophosphates were shown to undergo efficient self-templating ligation to higher oligomers with high sequence-, regio-, and chiro-selectivity. Tetramers with differing, but fitting, hemi-complementary base sequences can undergo stochastic co-oligomerization to give rise to large libraries of p-RNA sequences. The high chiroselectivity of the ligation process leads one to think of a scenario in which a comprehensively stochastic co-oligomerization process starting from the heterochiral and strictly racemic library of all eight possible diastereomers of all possible tetramer-2',3'-cyclophosphates (256 = 4 4 ) would necessarily break molecular mirror symmetry of higher oligomers in the sense that the resulting (equal amounts of) homochiral D-and L-libraries of a given (high) oligomer would not constitute a racemic mixture since the two libraries would have to have different sequence compositions by statistical reasons (Fig. 3).A thought-experiment in which this kind of capacity of an informational oligomer system is combined with a cap...

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l-α-Lyxopyranosyl (4‘→3‘) Oligonucleotides: A Base-Pairing System Containing a Shortened Backbone¹

Cited by 26 publications

References 12 publications

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

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

Chemical etiology of nucleic acid structure

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l-α-Lyxopyranosyl (4‘→3‘) Oligonucleotides: A Base-Pairing System Containing a Shortened Backbone1

Cited by 26 publications

References 12 publications

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

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

Chemical etiology of nucleic acid structure

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l-α-Lyxopyranosyl (4‘→3‘) Oligonucleotides: A Base-Pairing System Containing a Shortened Backbone¹