2′-Carbohydrate modifications in antisense oligonucleotide therapy: importance of conformation, configuration and conjugation
M Manoharan - Biochimica et Biophysica Acta (BBA)-Gene Structure …, 1999 - Elsevier
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 …
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 …