Oligonucleotides having R.sub.p and S.sub.p linkages at predetermined locations

• US 5,883,237 A
• Filed: 08/18/1993
• Issued: 03/16/1999
• Est. Priority Date: 08/05/1991
• Status: Expired due to Fees

• Current Assignee: Polish Academy of Science
• Original Assignee: Polish Academy of Science
• Inventors: Stec, Wojciech J., Grajkowski, Andrzej, Uznanski, Bogdan
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US08/108,878
• Time in Patent Office: 2,036 Days
• Field of Search: 536/23.1, 536/24.3, 536/24.5, 511/44
• US Class Current: 536/23.1
• CPC Class Codes: C07F 9/6564 having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
• CPC Class Codes: C07F 9/6578 having phosphorus and sulfur atoms with or without oxygen atoms, as ring hetero atoms
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• 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

Methods and compounds are provided for solid phase synthesis of oligonucleotides and related polymers by condensing protected monomer-O- 1,3,2-dichalcogen-substituted-phospholane! synthons in the presence of a catalytic base. Compounds of the invention include 2-N-substituted-1,3,2-dichalcogen-substituted-phospholane precursors of the above synthons, the protected monomer-O- 1,3,2-dichalcogen-substituted-phospholane! synthons, and P-chiral oligonucleotides and related P-chiral polymers.

Claims

1. A single-stranded oligonucleotide of predetermined length between 12 and 60 nucleotides inclusive, said nucleotides being linked by phosphorus linkages selected from the group consisting of phosphodiester, phosphorothioate and phosphorodithioate, a plurality of said phosphorus linkages having predetermined R_p or S_p chirality.

2. The oligonucleotide of claim 1, wherein said phosphorus linkages are phosphorothioate.

3. The oligonucleotide of claim 2 wherein all of said phosphorus linkages are R_p chiral.

4. The oligonucleotide of claim 2 wherein all of said phosphorus linkages are S_p chiral.

5. The oligonucleotide of claim 1, wherein the predetermined length is between 15 and 30 nucleotides, inclusive.

6. The oligonucleotide of claim 1, wherein the phosphorus linkages are alternating R_p and S_p linkages.

7. A single-stranded oligonucleotide containing a predetermined number of consecutive P-chiral 5'"'"' to 3'"'"' phosphorus linkages, wherein said predetermined number is an integer between 12 and 60 monomers inclusive, said phosphorous linkages are selected from the group consisting of phosphorothioate and phosphorodithioate, and each of said linkages has a predetermined Rp or Sp chirality.

8. The oligonucleotide of claim 7, wherein said linkages are P-chiral phosphorothioate linkages.

9. The oligonucleotide of claim 7, wherein said linkages are all S_p chiral.

10. The oligonucleotide of claim 7, wherein said linkages are all R_p chiral.

11. The oligonucleotide of claim 7, wherein said linkages are alternating R_p and S_p linkages.

12. The oligonucleotide of claim 7, wherein said predetermined number is between 15 and 30 inclusive.