Oligonucleotides containing 5-fluorouracil

• US 5,457,187 A
• Filed: 12/08/1993
• Issued: 10/10/1995
• Est. Priority Date: 12/08/1993
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Nebraska
• Original Assignee: Board of Regents of the University of Nebraska
• Inventors: Iversen, Patrick L., Gmeiner, William H.
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Kunz, Gary L.
• Application Number:
  US08/164,089
• Time in Patent Office: 671 Days
• Field of Search: 536/25.5, 514/50
• US Class Current: 536/25.5
• 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

A homo-oligonucleotide of between 2 and 26 monomers of 5-fluorouridine 5'"'"'-monophosphate or 5-fluorodeoxyuridine 5'"'"'-monophosphate covalently linked via 3'"'"'- to 5'"'"'-phosphodiester linkages, where at the 3'"'"'- or 5'"'"'- terminus there is covalently linked a molecule selected from the group consisting of cholesterol, ethyl-spaced adamatane, 1,2-di-hexadecylglycerol and poly-L-lysine. These homo-oligonucleotides exhibit antitumor activity.

Claims

1. A homo-oligonucleotide consisting essentially of between 2 and 26 monomers of 5-fluorodeoxyuridine 5'"'"'-monophosphate (FdUMP) covalently linked via 3'"'"'- to 5'"'"'-phosphodiester linkages, where at the 3'"'"'- or 5'"'"'-terminus there is covalently linked a molecule selected from the group consisting of cholesterol, ethyl-spaced adamatane, 1,2-di-hexadecylglycerol and poly-L-lysine.

2. The homo-oligonucleotide of claim 1 wherein said molecule is covalently linked only at the 3'"'"'-terminus.

3. The homo-oligonucleotide of claim 1 wherein said molecule is covalently linked only at the 5'"'"'-terminus.

4. A homo-oligonucleotide consisting essentially of between 2 and 26 monomers of 5-fluorouridine 5'"'"'-monophosphate (FUMP) covalently linked via 3'"'"'- to 5'"'"'-phosphodiester linkages, where at the 3'"'"'- or 5'"'"'-terminus there is covalently linked a molecule selected from the group consisting of cholesterol, ethyl-spaced adamatane, 1,2-dihexadecylglycerol and poly-L-lysine.

5. The homo-oligonucleotide of claim 4 wherein said molecule is covalently linked only at the 3'"'"'-terminus.

6. The homo-oligonucleotide of claim 4 wherein said molecule is covalently linked only at the 5'"'"'-terminus.

7. A homo-oligonucleotide consisting essentially of between 2 and 26 monomers of 5-fluorodeoxyuridine 5'"'"'-monophosphate (FdUMP) covalently linked via 3'"'"'- to 5'"'"'-phosphothioate linkages, where at the 3'"'"'- or 5'"'"'-terminus there is covalently linked a molecule selected from the group consisting of cholesterol, ethyl-spaced adamatane, 1,2-di-hexadecylglycerol and poly-L-lysine.

8. The homo-oligonucleotide of claim 7 wherein said molecule is covalently linked only at the 3'"'"'-terminus.

9. The homo-oligonucleotide of claim 7 wherein said molecule is covalently linked only at the 5'"'"'-terminus.

10. A homo-oligonucleotide consisting essentially of between 2 and 26 monomers of 5-fluorouridine 5'"'"'-monophosphate (FUMP) covalently linked via 3'"'"'- to 5'"'"'-phosphothioate linkages, where at the 3'"'"'- or 5'"'"'-terminus there is covalently linked a molecule selected from the group consisting of cholesterol, ethyl-spaced adamatane, 1,2-dihexadecylglycerol and poly-L-lysine.

11. The homo-oligonucleotide of claim 10 wherein said molecule is covalently linked only at the 3'"'"'-terminus.

12. The homo-oligonucleotide of claim 10 wherein said molecule is covalently linked only at the 5'"'"'-terminus.