Oligonucleotides with modified phosphate and modified carbohydrate moieties at the respective chain termini

• US 4,981,957 A
• Filed: 07/18/1985
• Issued: 01/01/1991
• Est. Priority Date: 07/19/1984
• Status: Expired due to Fees

• Current Assignee: Centre National De La Recherche Scientifique
• Original Assignee: Centre National De La Recherche Scientifique
• Inventors: Bayard, Bernard, Lebleu, Bernard
• Primary Examiner(s): Griffin, Ronald W.
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US06/756,369
• Time in Patent Office: 1,993 Days
• Field of Search: 514/46, 514/47, 536/27, 536/28, 536/29
• US Class Current: 536/25.2
• CPC Class Codes: A61P 31/12 Antivirals
• 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

The invention relates to novel oligonucleotides, the process for their preparation and their biological uses as mediators of the action of interferon. The oligonucleotides according to the invention have the formula: ##STR1## in which Y and T are identical or different and represent particularly O, S, Z and W are identical or different and represent particularly O, S, one at least of the elements Y and Z being different from oxygen, X represents particularly --CHOHCH₂ OH, Σ is a whole number equal to or greater than 2, A represents adenine or one of its derivatives. These oligonucleotides have antiviral use.

Claims

1. An oligonucleotide of the formula ##STR77## in which Y and T are identical or different and are O, S, Se or NH, Z and W are identical or different and are O, S or NH, at least one of the substituents Y and Z in at least one of the phosphate moieties being different from oxygen, X is selected from the group consisting of ##STR78## R is H or ##STR79## R₁ is alkyl of 1 to 5 carbon atoms or phenyl, Σ

is a whole number equal to

n when X is --CHOHCH₂ OR, or

n-1 when X is ##STR80## wherein n is an integer of 2 to 10, m is an integer of 1 to 3, and A is adenine or a derivative selected from the group consisting of ##STR81## and the physiologically acceptable salts thereof.

2. The oligonucleotide of claim 1, having the formula ##STR82## in which Y₁, Y₂, Y₃ and T are identical or different and are O, S, Se or NH and Z₁ and Z₂ are identical or different and are, O, S or NH, at least one of the substituents Y₁, Y₂, Y₃, Z₁ and Z₂ being different from oxygen.

3. The oligonucleotides of claim 1, having the formula ##STR83## in which Y₂, Y₃ and T are identical or different and are O, S, Se or NH, Z₂ is O, S or NH, at least one of the substituents Y₂, Y₃ and Z₂ being different from oxygen, R is hydrogen, and n is an integer between 2 to 10, inclusive.

4. The oligonucleotide of claim 1, having the formula ##STR84## in which Y₃ is S, Se or NH, T is O, S, Se or NH, R is hydrogen, and n is an integer between 2 and 10, inclusive.

5. The oligonucleotide of claim 1 in which T is oxygen.

6. The oligonucleotide of claim 2 in which T is oxygen.

7. The oligonucleotide of claim 3 in which T is oxygen.

8. The oligonucleotide of claim 4 in which T is oxygen.

9. The oligonucleotide of claim 1, wherein X is selected from the group consisting of ##STR85##

10. The oligonucleotide of claim 9, wherein Z and W are oxygen.

11. The oligonucleotide of claim 10, selected from the group consisting of oligonucleotides of the formulas ##STR86##

12. A pharmaceutical composition comprising the oligonucleotide of claim 9 and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising an oligonucleotide of claim 11 and a pharmaceutically acceptable carrier.