Bicyclonucleoside and oligonucleotide analogue

• US 6,770,748 B2
• Filed: 12/28/2001
• Issued: 08/03/2004
• Est. Priority Date: 03/07/1997
• Status: Expired due to Term

• Current Assignee: Exiqon A/S (Qiagen NV), Roche Innovation Center Copenhagen A/S (Roche Holding AG)
• Original Assignee: Takeshi Imanishi
• Inventors: Imanishi, Takeshi, Obika, Satoshi
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Crane, Lawrence E
• Application Number:
  US10/029,212
• Publication Number:
  US 20030105309A1
• Time in Patent Office: 949 Days
• Field of Search: 536/23.1, 536/26.7, 536/26.8, 536/26.9, 536/27.1, 536/28.4, 536/28.1, 536/27.2
• US Class Current: 536/23.1
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

An oligo- or polynucleotide analogue having one or more structures of the general formula

where B is a pyrimidine or purine nucleic acid base, or an analogue thereof,

is disclosed. The use of this analogue provides an oligonucleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.

Claims

1. A nucleoside analogue of the following formula (I):

where B is an analogue of pyrimidine or purine nucleic acid base, and X and Y are identical or different, and each represents a hydrogen atom, an alkyl group, an alkenyl group an alkynyl group, a cycloalkyl group, an aralkyl group, an aryl group, an acyl group, or a silyl group or a phosphoramidite.

2. A nucleoside analogue as claimed in claim 1, wherein X and Y each represents a hydrogen atom.

3. A mononucleoside amidite derivative as claimed in claim 1, wherein X is 4,4-dimethoxytrityl (DMTr), and Y is a 2(N,N-diisopropylcyanoethoxyphosphoramidityl).

4. An oligonucleotide or polynucleotide analogue having one or more structures of the formula (Ia):

where B is an analogue of a pyrimidine or purine nucleic acid base.

5. An oligonucleotide or polynucleotide analogue of the formula (II):

where B¹ and B are identical or different, and each represents an analogue of pyrimidine or purine nucleic acid base, R is a hydrogen acorn, a hydroxyl group, a halogen atom, or an alkoxy group,

W¹ and W² are identical or different, and each represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aralkyl group, an aryl group, an acyl group, a silyl group, a phosphoric acid residue, a naturally occurring nucleoside or a synthetic nucleoside bound via a phosphodiester bond, or an oligonucleotide or polynucelotide containing the nucleotide, n¹ or n² n are identical or different, and each denotes an integer of 0 to 50, and n³ is an integer of 1-50, provided that n¹ and n² n are not both zero, and that not all of the n² are zero at the same time and when n¹ and/or n² are or is 2 or more, B¹ and B need nor be identical, and R need not be identical.