Synthetic nucleosides and nucleotides. 37. Antisense oligodeoxynucleotides bearing 5-(phenylethyl)-2'-deoxyuridylate at the 3'-terminus: exonuclease-resistant molecule with natural phosphodiester backbone.
5-(Phenylethyl)-2'-deoxyuridine has been incorporated into an oligodeoxynucleotide (ODN) by using normal cyanoethyl phosphoramidite chemistry on a DNA synthesizer. For introduction of the modified residue at the 3'-end position of the ODN, we designed and synthesized a new nucleoside phosphoramidite derivative, which connected the 3'-hydroxyl group and phosphoramidite moiety by an alkaline-labile linker. The 3'-end could be substituted in ODNs by using commercially available supports as a starting material following standard NH4OH treatment. The ODN carrying 5-(phenylethyl)-2'-deoxyuridine at the 3'-end position showed about 3-fold resistance to nucleolytic degradation in human plasma without precluding its specific base-pairing activity.
Kawaguchi
T
T
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Yamaguchi
T
T
Tanaka
S
S
Tashiro
Y
Y
Saneyoshi
M
M
D003857:Deoxyuridine / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D005092:Exonucleases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry*
D004952:Esters; D016376:Oligonucleotides, Antisense; D009943:Organophosphorus Compounds; D005092:Exonucleases; D003857:Deoxyuridine