Synthesis and Characterization of Benzylidene Acetal-Type Bridged Nucleic Acids (BA-BNA)

Curr Protoc Nucleic Acid Chem. 2014 Sep 8:58:1.31.1-22. doi: 10.1002/0471142700.nc0131s58.

Abstract

Benzylidene acetal-type bridged nucleic acids (BA-BNAs) have a bridged structure that cleaves upon exposure to appropriate external stimuli, which induces changes in oligonucleotide properties. In particular, duplex stability and resistance to enzymatic digestion vary depending on the incorporation number and/or position of BA-BNAs. This unit describes the synthesis of some types of BA-BNA thymine nucleosides and the corresponding BA-BNA phosphoramidites, as well as the incorporation of BA-BNA nucleosides into oligonucleotides. Moreover, typical procedures that induce property changes in each BA-BNA are described. 6-Nitroveratrylidene and 2-nitrobenzylidene acetal type BA-BNA respond to photoirradiation and subsequent thiol treatment. Benzylidene and 4-nitrobenzylidene acetal type BA-BNAs respond to acids and reducing agents, respectively. Every BA-BNA is derivatized into 4'-C-hydroxymethyl RNA by hydrolysis of the acetal-bridged structure.

Keywords: acid-trigger; bridged nucleic acid (BNA); external stimuli; light-trigger; property change; redox-change-trigger; sugar-modified nucleoside.

Publication types

  • Review

MeSH terms

  • Benzylidene Compounds / chemistry*
  • Bridged-Ring Compounds / chemistry*
  • RNA / chemical synthesis*
  • RNA / chemistry*

Substances

  • Benzylidene Compounds
  • Bridged-Ring Compounds
  • RNA