Reinforced HNA Backbone Hydration in the Crystal Structure of a Decameric HNA/RNA Hybrid

Maier, Timm; Przylas, Ingo; Sträter, Norbert; Herdewijn, Piet

doi:10.1021/ja045843v

Cited by 30 publications

(30 citation statements)

References 46 publications

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“…As expected, all hexoses show a chair conformation, in line with the higher conformational preorganization of HNA than with DNA. However, a recent crystal structure of an HNA:RNA duplex (Figure 9) at 2.6Å resolution revealed four independent molecules per asymmetric unit that exhibit some conformational variations in their HNA strands (55). These structures also disclosed a reinforced hydration of HNA phosphate groups that might contribute to the high stability of HNA duplexes and hybrids between HNA and DNA or HNA and RNA.…”

Section: Hexitol Nucleic Acidmentioning

confidence: 96%

Insights from Crystallographic Studies into the Structural and Pairing Properties of Nucleic Acid Analogs and Chemically Modified DNA and RNA Oligonucleotides

Egli

Pallan

2007

Annu. Rev. Biophys. Biomol. Struct.

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Chemically modified nucleic acids function as model systems for native DNA and RNA; as chemical probes in diagnostics or the analysis of protein-nucleic acid interactions and in high-throughput genomics and drug target validation; as potential antigene-, antisense-, or RNAi-based drugs; and as tools for structure determination (i.e., crystallographic phasing), just to name a few. Biophysical and structural investigations of chemically modified DNAs and RNAs, particularly of nucleic acid analogs with more significant alterations to the well-known base-sugar-phosphate framework (i.e., peptide or hexopyranose nucleic acids), can also provide insights into the properties of the natural nucleic acids that are beyond the reach of studies focusing on DNA or RNA alone. In this review we summarize results from crystallographic analyses of chemically modified DNAs and RNAs that are primarily of interest in the context of the discovery and development of oligonucleotide-based therapeutics. In addition, we re-examine recent structural data on nucleic acid analogs that are investigated as part of a systematic effort to rationalize nature's choice of pentose in the genetic system.

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Section: Hexitol Nucleic Acidmentioning

confidence: 96%

Insights from Crystallographic Studies into the Structural and Pairing Properties of Nucleic Acid Analogs and Chemically Modified DNA and RNA Oligonucleotides

Egli

Pallan

2007

Annu. Rev. Biophys. Biomol. Struct.

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“…We also relied on other template sequences, among them the so-called Dickerson-Drew Dodecamer (DDD [45,47]) with sequence d(CGCGAATTCGCG) to analyze numerous nucleic acid modifications, both 2′-deoxyribonucleotide and ribonucleotide analogs. Ideally, template sequences yield crystals of the native and modified forms that diffract to high resolution, allowing detailed insights into the water structure and the coordination sites and modes of mono- and divalent metal cations and the polyamine spermine [48–56] (Fig. 4, Molecular graphics images were produced using the UCSF Chimera package [57]).…”

Section: Template Sequences For Crystallizationmentioning

confidence: 99%

Crystallographic Studies of Chemically Modified Nucleic Acids: A Backward Glance

Egli

Pallan

2010

Chemistry & Biodiversity

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Chemically modified nucleic acids (CNAs) are widely explored as antisense oligonucleotide or small interfering RNA (siRNA) candidates for therapeutic applications. CNAs are also of interest in diagnostics, high-throughput genomics and target validation, nanotechnology and as model systems in investigations directed at a better understanding of the etiology of nucleic acid structure as well as the physical-chemical and pairing properties of DNA and RNA and for probing protein-nucleic acid interactions. In this article we review research conducted by our laboratory over the past two decades with a focus on crystal structure analyses of CNAs and artificial pairing systems. We highlight key insights into issues ranging from conformational distortions as a consequence of modification to the modulation of pairing strength and RNA affinity by stereoelectronic effects and hydration. Although crystal structures have only been determined for a subset of the large number of modifications that were synthesized and analyzed in the oligonucleotide context to date, they have yielded guiding principles for the design of new analogs with tailormade properties, including pairing specificity, nuclease resistance and cellular uptake. And, perhaps less obviously, crystallographic studies of CNAs and synthetic pairing systems have shed light on fundamental aspects of DNA and RNA structure and function that would not have been disclosed by investigations solely focused on the natural nucleic acids.

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“…First, modified nucleotide monomers (d-CNA, l-CNA, and d-b-homo-DNA) were created in Macromodel [19] and energyminimized in the Amber* force field [20]. Quatfit [21] was then used to fit these modified nucleotides onto the template double helices HNA · RNA (pdb entry 2BJ6) [22] and p-RNA · p-RNA [23], respectively, as given in Table 3 [24].…”

Section: Experimental Partmentioning

confidence: 99%

Conformational and Chiral Selection of Oligonucleotides

Froeyen

Morvan

Vasseur

et al. 2007

Chemistry & Biodiversity

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In view of a better understanding of chiral selection of oligonucleotides, we have studied the hybridization of D- and L-CNA (cyclohexane nucleic acids) and D- and L-DNA, with chiral D-beta-homo-DNA and achiral PNA (peptide nucleic acids). PNA hybridizes as well with D-DNA, L-DNA as with D-beta-homo-DNA. The structure of the PNA x D-beta-homo-DNA complex is different from the PNA x DNA duplexes. D-CNA prefers D-DNA as hybridization partner, while L-CNA prefers D-beta-homo-DNA as hybridization partner. The conformation of the enantiomeric oligonucleotides D-CNA and L-CNA in the supramolecular complex with D-DNA and D-beta-homo-DNA, respectively, is different. These data may contribute to the confirmation of a hypothesis of the existence of achiral informative polymers as RNA predecessor, and to the understanding of homochirality of nucleic acids.

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Reinforced HNA Backbone Hydration in the Crystal Structure of a Decameric HNA/RNA Hybrid

Cited by 30 publications

References 46 publications

Insights from Crystallographic Studies into the Structural and Pairing Properties of Nucleic Acid Analogs and Chemically Modified DNA and RNA Oligonucleotides

Insights from Crystallographic Studies into the Structural and Pairing Properties of Nucleic Acid Analogs and Chemically Modified DNA and RNA Oligonucleotides

Crystallographic Studies of Chemically Modified Nucleic Acids: A Backward Glance

Conformational and Chiral Selection of Oligonucleotides

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