PNA-DNA-PNA chimeric macromolecules

• US 6,277,603 B1
• Filed: 07/01/1998
• Issued: 08/21/2001
• Est. Priority Date: 12/24/1991
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Cook, Phillip Dan
• Primary Examiner(s): Yucel, Remy
• Assistant Examiner(s): SCHMIDT, MARY M
• Application Number:
  US09/108,911
• Time in Patent Office: 1,147 Days
• Field of Search: 536/23.1, 536/24.5, 536/24.3, 435/6, 435/91.1, 435/325, 435/366, 514/44
• US Class Current: 435/91.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• 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
• CPC Class Codes: C07K 14/003 Peptide-nucleic acids (PNAs)
• CPC Class Codes: C07K 9/005 containing within the molecule the substructure with m, n > 0 and m+n > 0, A, B, D, E being heteroatoms; X being a bond or a chain, e.g. muramylpeptides
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/32 of the sugar
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3521 Methyl
• CPC Class Codes: C12N 2310/3531 Hydrogen
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6832 Enhancement of hybridisation reaction
• CPC Class Codes: C12Q 2521/319 Exonuclease
• CPC Class Codes: C12Q 2525/101 incorporating non-naturally occurring nucleotides, e.g. inosine
• CPC Class Codes: C12Q 2525/125 incorporating agents resulting in resistance to degradation

Abstract

Macromolecules are provided that have increased nuclease resistance, increasing binding affinity to a complementary strand, and that activate RNase H enzyme. The macromolecules have the structure PNA-DNA-PNA where the DNA portion is composed of subunits of 2′-deoxy-erythro-pento-furanosyl nucleotides and the PNA portions are composed of subunits of peptide nucleic acids. Such macromolecules are useful for diagnostics and other research purposes, for modulating protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to therapeutics.

Claims

1. A macromolecule of the structure:

2. A method of in vitro modification of RNA, comprising contacting a test solution containing RNase H and said RNA with a macromolecule of claim 1, thereby effecting modification of said RNA.

4. The method of claim 2 wherein said contacting effects modification of said RNA.

3. A method of in vitro modification of RNA, comprising contacting a test solution containing RNase H and said RNA with a compound having the structure:

5. The method of claim 3 wherein said contacting effects modification of said RNA.