The synthesis of oligoribonucleotides containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines via post-synthetic modification of precursor oligomers

Nucleic Acids Res. 2003 Aug 1;31(15):4461-71. doi: 10.1093/nar/gkg632.

Abstract

The N6-alkyladenosines and 2-methylthio-N6-alkyladenosines are the most common modified adenosine nucleosides and transfer ribonucleic acids (tRNA) are particularly rich in these modified nucleosides. They are present at position 37 of the anticodon arm and the contribution of these hypermodified nucleosides to codon-anticodon interactions, as well as translation, are significant, although not fully understood. Herein we described a new chemical synthesis method of the oligoribonucleotides containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines via post-synthetic modifications of precursor oligoribonucleotides. To obtain oligoribonucleotides containing N6-alkyladenosines, the precursor oligoribonucleotide carrying 6-methylthiopurine riboside residue was used, whereas for the synthesis of oligoribonucleotides containing 2-methylthio-N6-alkyladenosines the precursor oligoribonucleotide carrying the 2-methylthio-6-chloropurine riboside was applied. Among the modified oligoribonucleotides of different length and secondary structures, there were several containing naturally occurring modified nucleosides such as: N6-isopentenyladenosine (i6A), N6-methyladenosine (m6A), 2-methylthio-N6-isopentenyladenosine (ms2i6A), and 2-methylthio-N6-methyladenosine (ms2m6A), as well as several unnaturally modified adenosine derivatives.

Publication types

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

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry*
  • Alkylation
  • Amines / chemistry
  • Methylthioinosine / chemistry
  • Oligonucleotides / chemistry
  • Oligoribonucleotides / chemical synthesis*
  • Oligoribonucleotides / chemistry
  • Organophosphorus Compounds / chemistry
  • Oxidation-Reduction
  • Purine Nucleosides / chemistry
  • Sulfoxides / chemistry
  • Thionucleosides / chemical synthesis
  • Thionucleosides / chemistry*

Substances

  • Amines
  • Oligonucleotides
  • Oligoribonucleotides
  • Organophosphorus Compounds
  • Purine Nucleosides
  • Sulfoxides
  • Thionucleosides
  • phosphoramidite
  • Methylthioinosine
  • 2-methylthioadenosine
  • Adenosine