Solid Supports for the Synthesis of 3'-Aminooxy Deoxy- or Ribo-oligonucleotides and Their 3'-Conjugation by Oxime Ligation.

Mono- and triethylene glycol aminooxy derivatives were reacted with levulinic acid, protected with dimethoxytrityl, and immobilized on solid support. The resulting solid supports were used for elongation of oligonucleotides. Then, a mild ammonia treatment was applied to remove the oligonucleotide protecting groups, followed by a treatment with 50 mM methoxyamine at pH 4.2, releasing the 3'-aminooxy oligonucleotides by an oxime exchange reaction. The resulting 3'-aminooxy deoxy- or ribo-oligonucleotides were conjugated to various ketones and aldehydes with high efficiency by oxime ligation.