title: Synthesis of high quality phosphorothioate oligonucleotides as antisense drugs. Use of I-linker in the elimination of 3'-terminal phosphorothioate monoesters.
abstract: Detritylation of a 5'-O-DMT-2'-deoxyadenosine moiety attached to solid support under acidic condition leads to depurination during oligonucleotide synthesis. Deprotection followed by reversed phase HPLC purification leads to desired oligonucleotide contaminated with significant levels of 3'-terminal phosphorothiaote (3'-TPT) monoester (n-1)-mer. However, it is demonstrated that attachment of dA nucleoside through its exocyclic amino group to solid support leads to substantial reduction of 3'-TPT formation thereby improving the quality of oligonucleotide synthesized.
authors.affiliation: Isis Pharmaceuticals, Carlsbad, California 92009, USA. vravikumar@isisph.com
authors.forename: Vasulinga T
authors.initials: VT
authors.lastname: Ravikumar
authors.forename: R Krishna
authors.initials: RK
authors.lastname: Kumar
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Capaldi
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Cole
mesh_terms: D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D007202:Indicators and Reagents; D008968:Molecular Conformation; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry; D010710:Phosphates
chemical_list: D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D010710:Phosphates; C027903:oligo (dT)