Modified oligonucleotides: IV solid phase synthesis and preliminary evaluation of phosphorothioate RNA as potential antisense agents.

✍ Scribed by François Morvan; Bernard Rayner; Jean-Louis Imbach

• Book ID: 104228557
• Publisher: Elsevier Science
• Year: 1990
• Tongue: French
• Weight: 259 KB
• Volume: 31
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)97264-2

✦ Synopsis

For the first time a phosphorothioate oligoribonucleotide. namely PS-Cl4. has been synthesized on solid support. This modified oligomer is more resistant to enzymatic degradation than the corresponding rC14 and binds to complementary RNA strands.

Various series of modified oligodeoxynucleotides have been described in the last few years and shown to be more resistant to nuclease degradation than the natural DNA and to still bind to complementary nucleic acid sequences. 2 Among these series, phosphorothioate analogues of oligodeoxyribonucleotides (PS-DNA) seem to be of great interest due to their potent anti-HIV activities.3 Since modified RNAs4 have been less extensively explored than modified DNAs, except for a recent preliminary note on a-RNA synthesis5 and some publications on L-RNA6 we decided to prepare phosphorothioate oligoribonucleotides (PS-RNA), in order to determine if they could eventually be used as antisense agents. In this communication we describe the first synthesis on a solid support of a PS-RNA. namely PS-rC14 and report on its nuclease resistance and its base-pairing properties.

Automated syntheses of PS-DNAs have been previously performed by the Hphosphonate or phosphoramidite approach. In the latter case stepwise sulfurization with elemental sulfur7 causes technical problems.8 Very recently a new sulfurization reagent : 3H-1 .ZbenxodithioleS-one-l, l-dioxide, was introduced by Beaucage. and shown to lead, in