Patent ID: 6613894
Filing Date: 2003-09-02
Classification: A61K,C07H,G01N,Y02P,Y10S

Abstract:
A process for the preparation of a pyranosyl nucleic acid, comprising(a) bonding a 3â€²-, 4â€²-diprotected pyranosyl nucleoside to a solid phase by coupling of the 2â€²-OH with a CPG support or other similar support with an amide linkage; wherein the 3â€²-protective group is selected from the group consisting of an acetyl group, benzoyl group, nitrobenzoyl group, methoxybenzoyl group, other base-labile protective groups, and groups that can be removed with catalytic hydrogenolysis; wherein the 4â€²-protective group is selected from the group consisting of a trityl group, fluorenylmethyloxycarbonyl (FMOC) group, 4,4â€²-dimethoxytrityl (DMT) group, and other acid-labile protective groups; (b) deprotecting the 3â€²-, 4â€²-diprotected pyranosyl nucleoside bonded to the solid phase according to step (a) in the 4â€²-position, wherein the protective group is removed by reaction with an acid; (c) reacting the reaction product from step (b) with a 3â€²-, 4â€²-diprotected pyranosyl nucleoside 2â€²-phosphoramidite, wherein the reacting is performed under conditions including a reagent selected from the group consisting of pyridinium hydrochloride, benzimidazolium triflate, arylsulphonyl chlorides, diphenyl chlorophosphonate, pivaloyl chloride, and adamantoyl chloride; (d) oxidizing the reaction product of step (c); (e) repeating steps (b) through (d) one or more times to produce the desired length of nucleic acid; and (f) coupling a biomolecule to the product of step (e) while the product of step (b) is bound to the support, wherein the biomolecule is selected from the group consisting of DNA, RNA, peptide, protein, antibody, functional antibody fragment, and any other biologically active molecule under conditions where the biomolecule is not hybridized.