Solution structure and conformational dynamics of deoxyxylonucleic acids (dXNA) : an orthogonal nucleic acid candidate

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2012
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Maiti, Mohitosh
Lescrinier, Eveline
Rosemeyer, Helmut
Froeyen, Mathy
Ramaswamy, Amutha
Ceulemans, Arnout
Herdewijn, Piet
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Chemistry - A European Journal ; 18 (2012), 3. - pp. 869-879. - ISSN 0947-6539. - eISSN 1521-3765
Abstract
Orthogonal nucleic acids are chemically modified nucleic acid polymers that are unable to transfer information with natural nucleic acids and thus can be used in synthetic biology to store and transfer genetic information independently. Recently, it was proposed that xylose-DNA (dXNA) can be considered to be a potential candidate for an orthogonal system. Herein, we present the structure in solution and conformational analysis of two self-complementary, fully modified dXNA oligonucleotides, as determined by CD and NMR spectroscopy. These studies are the initial experimental proof of the structural orthogonality of dXNAs. In aqueous solution, dXNA duplexes predominantly form a linear ladderlike (type-1) structure. This is the first example of a furanose nucleic acid that adopts a ladderlike structure. In the presence of salt, an equilibrium exists between two types of duplex form. The corresponding nucleoside triphosphates (dXNTPs) were synthesized and evaluated for their ability to be incorporated into a growing DNA chain by using several natural and mutant DNA polymerases. Despite the structural orthogonality of dXNA, DNA polymerase b mutant is able to incorporate the dXNTPs, showing DNA-dependent dXNA polymerase activity.
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540 Chemistry
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DNA structures,helical structures,NMR spectroscopy,nucleic acids,orthogonal nucleic acids,synthetic biology
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ISO 690MAITI, Mohitosh, Vanessa SIEGMUND, Mikhail ABRAMOV, Eveline LESCRINIER, Helmut ROSEMEYER, Mathy FROEYEN, Amutha RAMASWAMY, Arnout CEULEMANS, Andreas MARX, Piet HERDEWIJN, 2012. Solution structure and conformational dynamics of deoxyxylonucleic acids (dXNA) : an orthogonal nucleic acid candidate. In: Chemistry - A European Journal. 18(3), pp. 869-879. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201102509
BibTex
@article{Maiti2012-01-16Solut-17519,
  year={2012},
  doi={10.1002/chem.201102509},
  title={Solution structure and conformational dynamics of deoxyxylonucleic acids (dXNA) : an orthogonal nucleic acid candidate},
  number={3},
  volume={18},
  issn={0947-6539},
  journal={Chemistry - A European Journal},
  pages={869--879},
  author={Maiti, Mohitosh and Siegmund, Vanessa and Abramov, Mikhail and Lescrinier, Eveline and Rosemeyer, Helmut and Froeyen, Mathy and Ramaswamy, Amutha and Ceulemans, Arnout and Marx, Andreas and Herdewijn, Piet}
}
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    <dcterms:abstract xml:lang="eng">Orthogonal nucleic acids are chemically modified nucleic acid polymers that are unable to transfer information with natural nucleic acids and thus can be used in synthetic biology to store and transfer genetic information independently. Recently, it was proposed that xylose-DNA (dXNA) can be considered to be a potential candidate for an orthogonal system. Herein, we present the structure in solution and conformational analysis of two self-complementary, fully modified dXNA oligonucleotides, as determined by CD and NMR spectroscopy. These studies are the initial experimental proof of the structural orthogonality of dXNAs. In aqueous solution, dXNA duplexes predominantly form a linear ladderlike (type-1) structure. This is the first example of a furanose nucleic acid that adopts a ladderlike structure. In the presence of salt, an equilibrium exists between two types of duplex form. The corresponding nucleoside triphosphates (dXNTPs) were synthesized and evaluated for their ability to be incorporated into a growing DNA chain by using several natural and mutant DNA polymerases. Despite the structural orthogonality of dXNA, DNA polymerase b mutant is able to incorporate the dXNTPs, showing DNA-dependent dXNA polymerase activity.</dcterms:abstract>
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