Phosphorothioate oligonucleotides hybridization

Zhang, R., Lu, Z., Zhao, H., Zhang, X., Diasio, R.B., Habus, I. et al. (1995b) In vivo stability, disposition, and metabolism of a hybrid oligonucleotide phosphorothioate in rats. Biochem. Pharmacol., 50, 545-556. 

Hoke GD, Draper K, Freier SM, et al. Effect of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection, Nucleic Acid Res 1991 20 5743-5748. 

Deverre JR, Boutet V, Boquet D, Ezan E, Grassi J, Grognet JM (1997) A competitive enzyme hybridization assay for plasma determination of phosphodiester and phosphorothioate anti-sense oligonucleotides. Nucleic Acids Res 25(18) 3584-3589... 

Mixed backbone hybrid oligonucleotides also have been made using methylphosphonate iinkages at the ends. Methyiphosphonates are nonionic, are resistant to nucleases, but do not lead to RNase H degradation. The reduced polyanionic nature of the mixed backbone oligonucleotide with methylphosphonate moieties have the potential to reduce the clotting abnormality associated with the use of phosphorothioate agents (14). 

Using an easy and versatile procedure for oligonucleotide-polyamine conjugation [46], polyamines were conjugated to distinct terminal and internal positions along nucleotide sequences. Upon poly amine attachment to terminal nucleosides, the hybridization efficiency with the complementary nucleotide sequence increased with the number of cationic amines. However, tethering to an internal nucleoside resulted in a considerable decrease in duplex stabihty. However, in phosphorothioates... 

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