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

J Org Chem. 2019 Nov 15;84(22):14854-14860. doi: 10.1021/acs.joc.9b00848. Epub 2019 Oct 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't