Recognition and detection of 8-oxo-rG in RNA using the DNA/OMeRNA chimera probes containing fluorescent adenosine-diazaphenoxazine analog

Bioorg Med Chem. 2016 Mar 15;24(6):1308-13. doi: 10.1016/j.bmc.2016.02.001. Epub 2016 Feb 2.

Abstract

Recent studies indicate that oxidative damage to RNA results in dysfunction of translation and eventual pathogenesis. A representative oxidized base in RNA is 8-hydroxyguanosine (8-oxo-rG), however, unlike its DNA counterpart (8-oxo-dG), its role in pathogenesis has not attracted much attention until recently. The 2'-deoxyadenosine derivative with a diazaphenoxazine skeleton at the 6-amino group (Adap) was shown to be selective for 8-oxo-dG in DNA. In this study, the 2'-O-methoxy derivative of Adap (2'-OMeAdap) was designed as a selective molecule for 8-oxo-rG in RNA. 8-Oxo-rG in the homopurine RNA was selectively recognized by the ODN probe incorporating Adap. In contrast, although it was not possible by the Adap-containing ODN prove due to the instability of the corresponding duplex, 8-oxo-rG in homopyrimidine RNA was selectively detected by the 2'-OMeRNA probe incorporating 2'-OMeAdap.

Keywords: 8-Oxo-guanosine; Chimera probe; Fluorescence quenching; Fluorescent nucleoside analog; Oxidative damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analysis
  • Adenosine / chemistry*
  • Aza Compounds / analysis
  • Aza Compounds / chemistry*
  • DNA / analysis
  • DNA / chemistry*
  • Fluorescent Dyes / analysis
  • Fluorescent Dyes / chemistry*
  • Guanosine / analogs & derivatives*
  • Guanosine / analysis
  • Guanosine / chemistry
  • Molecular Probes / analysis
  • Molecular Probes / chemistry*
  • Oxazines / analysis
  • Oxazines / chemistry*
  • RNA / chemistry*

Substances

  • 1,3-diazaphenoxazine
  • Aza Compounds
  • Fluorescent Dyes
  • Molecular Probes
  • Oxazines
  • Guanosine
  • 8-hydroxyguanosine
  • RNA
  • DNA
  • Adenosine