Synthesis and crystallographic analysis of 5-Se-thymidine DNAs

Org Lett. 2009 Jun 18;11(12):2503-6. doi: 10.1021/ol9004867.

Abstract

We investigated the possibility of the interaction of 5-CH(3) of thymidine and its 5'-phosphate backbone (C-H...O(-)-PO(3) interaction) in DNA via the insertion of the atomic probe (a selenium atom) into the exo-5-position of thymidine (5-Se-T). 5-Se-T was synthesized for the first time, via Mn(OAc)(3) assisted electrophilic addition of CH(3)SeSeCH(3) to 3',5'-di-O-benzoyl-2'-deoxyuridine. The 5-Se-T phosphoramidite was subsequently synthesized and incorporated into DNA in over 99% coupling yield. Biophysical and structural investigations of the 5-Se-T DNAs revealed that the Se-modified and nonmodified DNAs are virtually identical. In addition, the crystallographic analysis of a 5-Se-T DNA strongly suggests a hydrogen-bond formation between the 5-CH(3) and 5'-phosphate groups (CH(3)...PO(4)(-) interaction).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Crystallography, X-Ray / methods
  • DNA / chemical synthesis*
  • DNA / chemistry
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Structure
  • Nucleic Acid Conformation
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry
  • Organophosphorus Compounds / chemical synthesis
  • Organophosphorus Compounds / chemistry
  • Organoselenium Compounds / chemical synthesis*
  • Organoselenium Compounds / chemistry
  • Selenium / analysis*
  • Selenium / chemistry
  • Thymidine / chemical synthesis*
  • Thymidine / chemistry

Substances

  • Oligonucleotides
  • Organophosphorus Compounds
  • Organoselenium Compounds
  • DNA
  • Selenium
  • Thymidine