Unrefined synthetic preparations containing polynucleotide compounds

Abstract

The invention proposes a polynucleotide-containing preparation, a pharmaceutical preparation containing this preparation, and a method for polynucleotide synthesis. The method described in the invention is a solid-phase method for producing polynucleotides through continuous conjugation cycles involving at least one step of coupling a dinucleotide subunit into a free group at the 3' end of the growing chain. Polynucleotides consist of at least two nucleoside subunits linked together by phosphoramidate bonds N3'-T'5'. The method may include the steps (a) deprotecting the protected 3' amino group of the terminal nucleoside attached to the solid phase, this deprotection step creates a free 3' amino group; (b) exposing the free 3' amino group to a protected amino-dinucleotide-5'phosphoranulide dimer at the 3' position in the presence of a nucleophilic catalyst to create a phosphoramidide bond N3'-T'5' between the nucleosides; and (c) oxidation (e.g., addition of sulfur atoms) of the resulting bond. The pharmaceutical product made by the method of the invention may contain a smaller amount of one or more polynucleotide products (Nx). The invention also proposes a pharmaceutical product containing this polynucleotide product.