Watson−Crick Base-Pairing Properties of Tricyclo-DNA

Renneberg, Dorte; Leumann, Christian J.

doi:10.1021/ja025569+

Cited by 119 publications

(112 citation statements)

References 30 publications

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“…The stability of the duplexes in solution increases in the following order: RNA:DNA~DNA:DNA < DNA:RNA < RNA:RNA~tcDNA:DNA << tcDNA:RNA. This result confirms earlier thermal melting studies on tcDNA that demonstrate remarkable stability and selectivity of tcDNA for RNA complements [3]. The difference between the DNA:RNA and RNA:DNA heteroduplexes arises from the changing pyrimidine content of the DNA strand.…”

Section: Resultssupporting

confidence: 89%

“…The fact that backbone cleavage within the hybrid duplex only occurs in the tcDNA strand further evidences the weakness of the N-glycosidic bond in the modified nucleoside. As to the second effect, previously published thermodynamic data obtained from UV melting experiments [3] demonstrate that the formation entropy of tcDNA duplexes in solution is reduced relative to nonmodified structures. Therefore, entropic stabilization of the hybrid duplexes should be assumed in the gas-phase.…”

Section: Parallel Fragmentation Channels In Tcdna:dna Heteroduplexesmentioning

confidence: 95%

“…A single tcDNA modification in a DNA:RNA heteroduplex with 12 base pairs can increase the melting temperature by up to +3.1°C. For fully modified tcDNA oligonucleotides, a stabilization of +2.4°C per modification was observed relative to the DNA:RNA hybrid [3]. The higher stability of the tcDNA-hybrids was found to arise from the decreased formation entropy of the modified duplexes attributed to the prearranged structure of the tcDNA single strand.…”

Section: Introduction Tcdna In Antisense Therapymentioning

confidence: 92%

“…The higher stability of the tcDNA-hybrids was found to arise from the decreased formation entropy of the modified duplexes attributed to the prearranged structure of the tcDNA single strand. Moreover, crystallographic data [4], CD spectroscopic analysis, and molecular dynamics simulations [3] suggest that…”

Section: Introduction Tcdna In Antisense Therapymentioning

confidence: 99%

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The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes

Hari

Dugovic

Istrate

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. Tricyclo-DNA (tcDNA) is a sugar-modified analogue of DNA currently tested for the treatment of Duchenne muscular dystrophy in an antisense approach. Tandem mass spectrometry plays a key role in modern medical diagnostics and has become a widespread technique for the structure elucidation and quantification of antisense oligonucleotides. Herein, mechanistic aspects of the fragmentation of tcDNA are discussed, which lay the basis for reliable sequencing and quantification of the antisense oligonucleotide. Excellent selectivity of tcDNA for complementary RNA is demonstrated in direct competition experiments. Moreover, the kinetic stability and fragmentation pattern of matched and mismatched tcDNA heteroduplexes were investigated and compared with non-modified DNA and RNA duplexes. Although the separation of the constituting strands is the entropy-favored fragmentation pathway of all nucleic acid duplexes, it was found to be only a minor pathway of tcDNA duplexes. The modified hybrid duplexes preferentially undergo neutral base loss and backbone cleavage. This difference is due to the low activation entropy for the strand dissociation of modified duplexes that arises from the conformational constraint of the tc-sugar-moiety. The low activation entropy results in a relatively high free activation enthalpy for the dissociation comparable to the free activation enthalpy of the alternative reaction pathway, the release of a nucleobase. The gas-phase behavior of tcDNA duplexes illustrates the impact of the activation entropy on the fragmentation kinetics and suggests that tandem mass spectrometric experiments are not suited to determine the relative stability of different types of nucleic acid duplexes.

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Section: Resultssupporting

confidence: 89%

Section: Parallel Fragmentation Channels In Tcdna:dna Heteroduplexesmentioning

confidence: 95%

Section: Introduction Tcdna In Antisense Therapymentioning

confidence: 92%

Section: Introduction Tcdna In Antisense Therapymentioning

confidence: 99%

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The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes

Hari

Dugovic

Istrate

et al. 2016

J. Am. Soc. Mass Spectrom.

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“…Les AON-tcDNA, analogues synthétiques de l'ADN, s'hybrident avec une très haute affinité avec leurs ARN pré-messagers cibles afin d'en moduler l'épissage et restaurer un cadre de lecture opérationnel éventuel-lement perturbé par une mutation [6,7] (Figure 1). Dans le cas de la souris mdx (modèle murin de DMD), ils permettent la synthèse d'une dystrophine certes tronquée, mais suffisamment stable et fonctionnelle pour entraîner un bénéfice thérapeutique.…”

Section: Une Nouvelle Génération D'oligonucléotides Antisensunclassified

Un nouvel outil pour le traitement de la myopathie de Duchenne : les tricyclo-ADN

et al. 2015

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Nucleic Acids

Rehmann¹

2005

Kirk-Othmer Encyclopedia of Chemical Technology

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Nucleic acids are essential components of all organisms. Deoxyribonucleic acids (DNA), most commonly double helical, encode the genetic information contained in living cells. Ribonucleic acids (RNA), a more diverse class of biopolymers able to adopt helical and other more complex tertiary structures, carry out a variety of intracellular functions, including transmitting the genetic message to the site of protein synthesis. Both DNA and RNA interact with a host of other molecules, eg, proteins, drugs, as well as other nucleic acids and nucleic acid constituents. The specificity of these interactions may be related to local sequence‐dependent structural variation. The structural characteristics of nucleic acids and their constituents are discussed. Development of techniques to synthesize oligonucleotides, which are short, well‐defined sequences of DNA or RNA, provides an opportunity to study nucleic acid structure in detail. In addition, oligonucleotides have proved invaluable in analytical procedures. The unique ability of nucleic acids to bind to self‐complementary sequences has been exploited in the design of oligonucleotide probes and in antisense drug strategies. Methods for synthesizing Oligonucleotides, including both unmodified and modified analogs are discussed.

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Watson−Crick Base-Pairing Properties of Tricyclo-DNA

Cited by 119 publications

References 30 publications

The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes

The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes

Un nouvel outil pour le traitement de la myopathie de Duchenne : les tricyclo-ADN

Nucleic Acids

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