2'-carbohydrate modifications in antisense oligonucleotide therapy: importance of conformation, configuration and conjugation

Biochim Biophys Acta. 1999 Dec 10;1489(1):117-30. doi: 10.1016/s0167-4781(99)00138-4.


The 2'-position of the carbohydrate moiety has proven to be a fertile position for oligonucleotide modifications for antisense technology. The 2'-modifications exhibit high binding affinity to target RNA, enhanced chemical stability and nuclease resistance and increased lipophilicity. All high binding affinity 2'-modifications have C3'-endo sugar pucker. In addition to gauche effects, charge effects are also important in determining the level of their nuclease resistance. Pharmacokinetic properties of oligonucleotides are altered by 2'-conjugates. For certain modifications (e.g., 2'-F), the configuration at the 2'-position, arabino vs. ribo, determines their ability to activate the enzyme RNase H.

Publication types

  • Review

MeSH terms

  • Alternative Splicing / drug effects
  • Amines / chemistry
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Carbohydrates / chemistry*
  • Cross-Linking Reagents / chemistry
  • Drug Design*
  • Enzyme Activation / drug effects
  • Molecular Conformation
  • Nucleic Acid Conformation / drug effects
  • Oligonucleotides, Antisense / chemistry*
  • Oligonucleotides, Antisense / pharmacokinetics
  • Oligonucleotides, Antisense / pharmacology
  • RNA, Messenger / metabolism
  • Ribonuclease H / metabolism
  • Sulfhydryl Compounds / chemistry


  • Amines
  • Carbohydrates
  • Cross-Linking Reagents
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Sulfhydryl Compounds
  • Ribonuclease H