Peptide nucleic acids

• US 5,539,082 A
• Filed: 04/26/1993
• Issued: 07/23/1996
• Est. Priority Date: 04/26/1993
• Status: Expired due to Term

• Current Assignee: Michael Egholm, Ole Buchardt, Peter E. Nielsen, Rolf H. Berg
• Original Assignee: Michael Egholm, Ole Buchardt, Peter E. Nielsen, Rolf H. Berg
• Inventors: Egholm, Michael, Nielsen, Peter E., Buchardt, Ole, Berg, Rolf H.
• Primary Examiner(s): Walsh, Stephen G.
• Application Number:
  US08/054,363
• Time in Patent Office: 1,184 Days
• Field of Search: 530/300, 514/2, 514/8, 514/44, 562/575, 544/242, 544/264, 536/24.3, 536/18.7
• US Class Current: 530/300
• 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: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• 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 5/06026 the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/15 Nucleic acids forming more than 2 strands, e.g. TFOs
• CPC Class Codes: C12N 2310/3181 Peptide nucleic acid, PNA
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2525/107 incorporating a peptide nucleic acid
• CPC Class Codes: C12Q 2535/107 Maxam and Gilbert method, i.e. sequential release and detection of nucleotides
• CPC Class Codes: C12Q 2537/119 Triple helix formation

Abstract

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

Claims

1. A compound having the formula:

##STR8## wherein;

each L is independently selected from the group consisting of hydrogen, phenyl, heterocyclic moleties, naturally occurring nucleobases, and non-naturally occurring nucleobases;

each R³ is independently selected from the group consisting of hydrogen, (C₁ -C₄)alkyl, hydroxy- or alkoxy- or alkylthio-substituted (C₁ -C₄)alkyl, hydroxy, alkoxy, alkylthio and amino;

each R^7'"'"' is independently selected from the group consisting of hydrogen and the side chains of naturally occurring alpha amino acids;

n is an integer from 1 to 60,

each k, l, and m is, independently, zero or an integer from 1 to 5;

each p is zero or 1;

R^h is OH, NH₂ or --NHLysNH₂ ; and

Rⁱ is H or COCH₃.

2. A compound having the formula:

##STR9## wherein;

each L is independently selected from the group consisting of hydrogen, phenyl, heterocyclic moieties, naturally occurring nucleobases, and non-naturally occurring nucleobases;

each R³ is independently selected from the group consisting of hydrogen, (C₁ -C₄)alkyl, hydroxy- or alkoxy- or alkylthio-substituted (C₁ -C₄)alkyl, hydroxy, alkoxy, alkylthio and amino;

each R^7'"'"' is independently selected from the group consisting of hydrogen and the side chains of naturally occurring alpha amino acids;

n is an integer from 1 to 60,

each k, l, and m is, independently, zero or an integer from 1 to 5;

each p is zero or 1;

R^h is OH, NH₂ or --NHLysNH₂ ; and

Rⁱ is H or COCH₃.

3. A compound having the formula:

##STR10## wherein;

L is independently selected from the group consisting of hydrogen, phenyl, heterocyclic moieties, naturally occurring nucleobases, and non-naturally occurring nucleobases;

R³ is selected from the group consisting of hydrogen, (C₁ -C₄) alkyl, hydroxy- or alkoxy- or alkylthio-substituted (C₁ -C₄) alkyl, hydroxy, alkylthio and amino;

each R^7'"'"' is independently selected from the group consisting of hydrogen and the side chains of naturally occurring alpha amino acids;

k, l, and m are, independently, zero or an integer from 1 to 5; and

p is zero or 1.