Synthesis of chimeric oligonucleotides containing phosphodiester, phosphorothioate, and phosphoramidate linkages.
[reaction: see text] H-Phosphonate monomers of 2'-O-(2-methoxyethyl) ribonucleosides have been synthesized. Oxidation of oligonucleotide H-phosphonates has been optimized to allow the synthesis of oligonucleotides containing either 2'-deoxy or 2'-O-(2-methoxyethyl) ribonucleoside residues combined with three different phosphate modifications in the backbone, i.e., phosphodiester (PO), phosphorothioate (PS), and phosphoramidate (PN). Phosphodiester linkages were introduced by oxidation with a cocktail of 0.1 M Et(3)N in CCl(4)/Pyr/H(2)O (5:9:1) without affecting phosphorothioate or phosphoramidate linkages. For the synthesis of phosphoramidate-modified oligonucleotides, N(4)-acetyl deoxycytidine-3'-H-phosphonate monomers were used to avoid transamination during the oxidation step.
Maier
M A
MA
Department of Medicinal Chemistry, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, California 92008, USA.
Guzaev
A P
AP
Manoharan
M
M
D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013873:Thionucleotides / Q000737:chemistry
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D009946:Organothiophosphorus Compounds; D013873:Thionucleotides