Solid Supports for the Synthesis of 3-Aminooxy Deoxy- or Ribo-oligonucleotides and Their 3-Conjugation by Oxime Ligation [component]

Mono-and tri-ethyleneglycol aminooxy derivatives were reacted with levulinic acid, protected with dimethoxytrityl and immobilized on long-chain alkylamine controlled-pore glass (LCAA-CPG) solid support. The resulting solid supports were used to synthesize 3'aminooxy oligonucleotides having a shorter or longer spacer between the oligonucleotide and the aminooxy function. After completion of oligonucleotide synthesis, a first-step mild ammonia treatment was applied to remove the oligonucleotide
more » ... otecting groups, followed by 2 a second-step treatment with 50 mM methoxyamine at pH 4.2, releasing the 3'-aminooxy oligonucleotides from the solid support by an oxime exchange reaction. The resulting 3'aminooxy deoxy-or ribo-oligonucleotides were conjugated to various ketones (acetone, fluorenone, cyclohexanone) and aldehydes (pyrene, deoxycholic, biotin) with high efficiency by means of oxime ligation.
doi:10.1021/acs.joc.9b00848.s001 fatcat:ncpnql5uqnbefalgcfumvhouym