Properties of phosphorothioate DNA analogs. An ab initio study of prototype model linkages derived from dimethyl-phosphate anion

Fabio Pichierri, Akinori Sarai

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Ab initio HF and MP2 calculations on prototype model linkages of phosphorothioate DNA backbones illuminate the effects of phosphorothioation on electronic and structural properties of DNA backbone. The replacement of a bridging oxygen atom by sulfur in the phosphodiester linkage is energetically favored over that of replacement of a non-bridging oxygen atom. In phosphorothioate derivatives containing the P(OS)(nb) moiety, the non- bridging oxygen atom always bears a higher negative charge than the non- bridging sulfur. Additional calculations on protonated (neutral) adducts suggest that phosphorothioation of the phosphodiester linkage lowers its proton affinity. Moreover, protonation of the non-bridging oxygen atom at phosphorous is favored over the protonation of the non-bridging sulfur atom for linkages containing the P(OS)(nb) moiety. The ab initio calculated structural parameters are compared to the available crystallographic data of small phosphorothioate molecules and phosphorothioate oligodeoxynucleotides. These results have implications upon the biological activity of phosphorothioate DNA analogs.

Original languageEnglish
Pages (from-to)103-116
Number of pages14
JournalJournal of Molecular Structure: THEOCHEM
Volume460
Issue number1-3
DOIs
Publication statusPublished - 1999 Feb 26
Externally publishedYes

Keywords

  • Ab initio MO calculations
  • Antisense drugs
  • Phosphorothioate DNA

ASJC Scopus subject areas

  • Biochemistry
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

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