US 4,401,796 A · Solid-phase synthesis of polynucleotides

Abstract

A resin support formed from a suitable resin such as polystyrene or a silica gel may be provided by forming an amino resin and by reacting the amino resin with an activated ester of a nucleoside to obtain the dimethoxytrityl resin. To add each successive nucleotide to the resin support, the nucleoside is phosphorylated to provide a monotriazolide. The phosphorylation may be provided by the reaction of a phosphoditriazolide with a 3'-hydroxyl neucleoside. The dimethoxytrityl resin is then hydroxylated to substitute the hydroxyl group for the dimethoxytrityl group in the resin support. The monotriazolide is then reacted with the hydroxylated resin support to provide the dimethoxytrityl resin. This reaction may occur in the presence of a nucleophilic catalyst, such as a catalyst selected from a group consisting of dimethylaminopyridine, N'-methylimidazole and tetrazole. A hydroxyl group may be then substituted again for the dimethoxytrityl group in the dimethoxytrityl resin to provide for the addition of other nucleotides to the resin support. The procedure may be repeated to provide polynucleotides with extended chains of nucleotides.

Claims51

Dependent claims

A method of forming a polynucleotide, including the following steps:

providing a resin support,
phosphorylating a nucleoside to provide a monotriazolide,
combining the monotriazolide with the resin support to provide a dimethoxytrityl resin, and
substituting a hydroxyl group for the dimethoxytrityl group in the dimethoxytrityl resin to provide the polynucleotide.

1 more element

Dependencies are inferred from the claim text.

Solid-phase synthesis of polynucleotides

Life of this patent

Solid-phase synthesis of polynucleotides

Life of this patent

Abstract

Claims51