Heteroatomic oligonucleoside linkages

• US 5,623,070 A
• Filed: 02/27/1995
• Issued: 04/22/1997
• Est. Priority Date: 07/27/1990
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Cook, Phillip D., Sanghvi, Yogesh S.
• Primary Examiner(s): Elliott, George C.
• Assistant Examiner(s): LARSON, THOMAS GEORGE
• Application Number:
  US08/395,168
• Time in Patent Office: 785 Days
• Field of Search: 536/23.1, 536/24.1, 536/25.3, 536/24.5, 536/27.14, 536/27.21, 536/27.23, 536/27.3, 536/27.6, 536/27.8, 536/27.81, 536/28.4, 536/28.2, 536/28.5 , 536/28.53, 536/28.54
• US Class Current: 536/27.6
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/605 the macromolecule containing phosphorus in the main chain, e.g. poly-phosphazene
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• 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 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

Oligonucleotide-mimicking macromolecules that have improved nuclease resistance are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligonucleotides with three or four atom linking groups provide unique oligonucleotide-mimicking macromolecules that are useful in regulating RNA expression and in therapeutics. Methods of synthesis and use also are disclosed.

Claims

1. A nucleoside of the structure:

##STR4## wherein Y₁ is CH₂ ;

Y₂ is aminooxy, alkylamino having 1 carbon atom, or alkenyl having 2 carbon atoms;

Z is H, OH, O--R'"'"'", amino, methyleneamino or phthalimido;

R'"'"'" is a hydroxyl blocking group;

X is H or OH;

Q is O; and

Bx is a heterocyclic base moiety.

2. The nucleoside of claim 1 wherein Y₂ is aminooxy.

3. The nucleoside of claim 1 wherein Y₂ is alkylamino having 1 carbon atom.

4. The nucleoside of claim 1 wherein Y₂ is alkenyl having 2 carbon atoms.

5. The nucleoside of claim 1 wherein Z is OH.

6. The nucleoside of claim 1 wherein Z is amino.

7. The nucleoside of claim 1 wherein Z is methyleneamino.

8. The nucleoside of claim 1 wherein Z is phthalimido.