Electronic Structures of LNA Phosphorothioate Oligonucleotides

Henrik G. Bohr, Irene Shim, Cy Stein, Henrik Ørum, Henrik F. Hansen, Troels Koch

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Important oligonucleotides in anti-sense research have been investigated in silico and experimentally. This involves quantum mechanical (QM) calculations and chromatography experiments on locked nucleic acid (LNA) phosphorothioate (PS) oligonucleotides. iso-potential electrostatic surfaces are essential in this study and have been calculated from the wave functions derived from the QM calculations that provide binding information and other properties of these molecules. The QM calculations give details of the electronic structures in terms of e.g., energy and bonding, which make them distinguish or differentiate between the individual PS diastereoisomers determined by the position of sulfur atoms. Rules are derived from the electronic calculations of these molecules and include the effects of the phosphorothioate chirality and formation of electrostatic potential surfaces. Physical and electrochemical descriptors of the PS oligonucleotides are compared to the experiments in which chiral states on these molecules can be distinguished. The calculations demonstrate that electronic structure, electrostatic potential, and topology are highly sensitive to single PS configuration changes and can give a lead to understanding the activity of the molecules.
Original languageEnglish
JournalMolecular Therapy-Nucleic Acids
Volume8
Pages (from-to)428-441
ISSN2162-2531
DOIs
Publication statusPublished - 2017

Bibliographical note

This is an open access article under the CC BY-NC-ND license.

Keywords

  • LNA phosphorothioate
  • DNA/LNA oligonucleotide
  • Diastereoisomers
  • Hartree-Fock calculations
  • Iso-potential surface
  • Anion chromatograms

Cite this

Bohr, Henrik G. ; Shim, Irene ; Stein, Cy ; Ørum, Henrik ; Hansen, Henrik F. ; Koch, Troels. / Electronic Structures of LNA Phosphorothioate Oligonucleotides. In: Molecular Therapy-Nucleic Acids. 2017 ; Vol. 8. pp. 428-441.
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abstract = "Important oligonucleotides in anti-sense research have been investigated in silico and experimentally. This involves quantum mechanical (QM) calculations and chromatography experiments on locked nucleic acid (LNA) phosphorothioate (PS) oligonucleotides. iso-potential electrostatic surfaces are essential in this study and have been calculated from the wave functions derived from the QM calculations that provide binding information and other properties of these molecules. The QM calculations give details of the electronic structures in terms of e.g., energy and bonding, which make them distinguish or differentiate between the individual PS diastereoisomers determined by the position of sulfur atoms. Rules are derived from the electronic calculations of these molecules and include the effects of the phosphorothioate chirality and formation of electrostatic potential surfaces. Physical and electrochemical descriptors of the PS oligonucleotides are compared to the experiments in which chiral states on these molecules can be distinguished. The calculations demonstrate that electronic structure, electrostatic potential, and topology are highly sensitive to single PS configuration changes and can give a lead to understanding the activity of the molecules.",
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Electronic Structures of LNA Phosphorothioate Oligonucleotides. / Bohr, Henrik G.; Shim, Irene; Stein, Cy; Ørum, Henrik; Hansen, Henrik F.; Koch, Troels.

In: Molecular Therapy-Nucleic Acids, Vol. 8, 2017, p. 428-441.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Electronic Structures of LNA Phosphorothioate Oligonucleotides

AU - Bohr, Henrik G.

AU - Shim, Irene

AU - Stein, Cy

AU - Ørum, Henrik

AU - Hansen, Henrik F.

AU - Koch, Troels

N1 - This is an open access article under the CC BY-NC-ND license.

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N2 - Important oligonucleotides in anti-sense research have been investigated in silico and experimentally. This involves quantum mechanical (QM) calculations and chromatography experiments on locked nucleic acid (LNA) phosphorothioate (PS) oligonucleotides. iso-potential electrostatic surfaces are essential in this study and have been calculated from the wave functions derived from the QM calculations that provide binding information and other properties of these molecules. The QM calculations give details of the electronic structures in terms of e.g., energy and bonding, which make them distinguish or differentiate between the individual PS diastereoisomers determined by the position of sulfur atoms. Rules are derived from the electronic calculations of these molecules and include the effects of the phosphorothioate chirality and formation of electrostatic potential surfaces. Physical and electrochemical descriptors of the PS oligonucleotides are compared to the experiments in which chiral states on these molecules can be distinguished. The calculations demonstrate that electronic structure, electrostatic potential, and topology are highly sensitive to single PS configuration changes and can give a lead to understanding the activity of the molecules.

AB - Important oligonucleotides in anti-sense research have been investigated in silico and experimentally. This involves quantum mechanical (QM) calculations and chromatography experiments on locked nucleic acid (LNA) phosphorothioate (PS) oligonucleotides. iso-potential electrostatic surfaces are essential in this study and have been calculated from the wave functions derived from the QM calculations that provide binding information and other properties of these molecules. The QM calculations give details of the electronic structures in terms of e.g., energy and bonding, which make them distinguish or differentiate between the individual PS diastereoisomers determined by the position of sulfur atoms. Rules are derived from the electronic calculations of these molecules and include the effects of the phosphorothioate chirality and formation of electrostatic potential surfaces. Physical and electrochemical descriptors of the PS oligonucleotides are compared to the experiments in which chiral states on these molecules can be distinguished. The calculations demonstrate that electronic structure, electrostatic potential, and topology are highly sensitive to single PS configuration changes and can give a lead to understanding the activity of the molecules.

KW - LNA phosphorothioate

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KW - Diastereoisomers

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KW - Anion chromatograms

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