title: Synthesis of chimeric oligonucleotides containing phosphodiester, phosphorothioate, and phosphoramidate linkages.
abstract: [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.
authors.affiliation: Department of Medicinal Chemistry, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, California 92008, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Maier
authors.forename: A P
authors.initials: AP
authors.lastname: Guzaev
authors.forename: M
authors.initials: M
authors.lastname: Manoharan
mesh_terms: 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
chemical_list: D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D009946:Organothiophosphorus Compounds; D013873:Thionucleotides