Synthesis and incorporation of the phosphoramidite derivative of 2'-O-photocaged 3'-s-thioguanosine into oligoribonucleotides: substrate for probing the mechanism of RNA catalysis

J Org Chem. 2014 Apr 18;79(8):3647-52. doi: 10.1021/jo4028374. Epub 2014 Mar 31.


Oligoribonucleotides containing 3'-S-phosphorothiolate linkages possess properties that can reveal deep mechanistic insights into ribozyme-catalyzed reactions. "Photocaged" 3'-S- RNAs could provide a strategy to stall reactions at the chemical stage and release them after assembly steps have occurred. Toward this end, we describe here an approach for the synthesis of 2'-O-(o-nitrobenzyl)-3'-thioguanosine phosphoramidite starting from N(2)-isobutyrylguanosine in nine steps with 10.2% overall yield. Oligonucleotides containing the 2'-O-(o-nitrobenzyl)-3'-S-guanosine nucleotide were then constructed, characterized, and used in a nuclear pre-mRNA splicing reaction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Guanosine / analogs & derivatives*
  • Guanosine / chemical synthesis
  • Guanosine / chemistry
  • Molecular Probes / chemical synthesis*
  • Molecular Probes / chemistry
  • Nucleic Acid Conformation
  • Oligoribonucleotides / chemistry*
  • Organophosphorus Compounds / chemical synthesis*
  • Phosphates / chemical synthesis*
  • Phosphates / chemistry
  • RNA Splicing
  • RNA, Catalytic / chemistry*


  • 2'-O-(o-nitrobenzyl)-3'-thioguanosine phosphoramidite
  • 3'-S-phosphorothiolate
  • Molecular Probes
  • Oligoribonucleotides
  • Organophosphorus Compounds
  • Phosphates
  • RNA, Catalytic
  • phosphoramidite
  • Guanosine