Modified oligonucleotides

• US 5,112,963 A
• Filed: 11/14/1988
• Issued: 05/12/1992
• Est. Priority Date: 11/12/1987
• Status: Expired due to Fees

• Current Assignee: Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Original Assignee: Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Inventors: Pieles, Uwe, Cramer, Friedrich, Englisch, Uwe
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): Tsung, Frederick F.
• Application Number:
  US07/270,243
• Time in Patent Office: 1,275 Days
• Field of Search: 536/27, 536/29, 435/6
• US Class Current: 536/25.32
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical

Abstract

The present invention provides modified oligonucleotides, wherein, amongst the first four bases on the 5'"'"'-end, they have the base sequence AT or TA and, bound to one of the two O^- groups of the 5'"'"'-phosphate group of the first nucleotide at the 5'"'"'-end of said oligonucleotide, they contain a radical of the general formula: ##STR1## in which R₄ is a spacer group and R₁, R₂ and R₃ are hydrogen atoms or alkyl or alkoxy radicals containing up to 3 carbon atoms.

These modified oligonucleotides can be used for blocking the replication and/or expression of genes which have a sequence complementary with the modified oligonucleotides.

Claims

1. A modified oligonucleotide characterized by having a base sequence AT or TA among the first two bases on its 5'"'"'-end and further characterized by having bound to one of the O^- radicals of the 5'"'"'-phosphate group of the first nucleotide at the 5'"'"'end of said oligonucleotide a moiety of the formula:

##STR7## wherein R₄ is an ethylene spacer group and R₁, R₂, and R₃, which may be the same or different are hydrogen or C₁ -C₃ alkyl or C₁ -C₃ alkoxy with the proviso that not every phosphate moiety of said oligonucleotide is substituted by a methyl group.

2. Modified oligonucleotide of claim 1 wherein at least one O^- radical of said oligonucleotide of replaced by an S^- radical.

3. Modified oligonucleotide of claim 1, wherein the oligonucleotide has a chain length of 8 to 50 nucleotides.

4. Modified oligonucleotide of claim 1, wherein R₁, R₂ and R₃ are methyl radicals.

5. Oligonucleotide of claim 1 wherein said oligonucleotide is complimentary to the sequence of the target nucleic acid.